hydroxyprostaglandin dehydrogenases

Summary

Summary: Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.

Top Publications

  1. ncbi Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer
    Michael Stanbrough
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cancer Res 66:2815-25. 2006
  2. pmc Inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3): overview and structural insights
    Michael C Byrns
    Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, 130C John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, United States
    J Steroid Biochem Mol Biol 125:95-104. 2011
  3. ncbi Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity
    K Matsuura
    Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, 502 8585, Japan
    J Biochem 124:940-6. 1998
  4. doi β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells
    Helena J M Smartt
    Cancer Research UK Colorectal Tumour Biology Research Group, School of Cellular and Molecular Medicine, University Walk, University of Bristol, Bristol, UK
    Gut 61:1306-14. 2012
  5. doi Induction of 1C aldoketoreductases and other drug dose-dependent genes upon acquisition of anthracycline resistance
    Zachary W Veitch
    Department of Biology, Laurentian University, Northern Ontario School of Medicine, Sudbury, Canada
    Pharmacogenet Genomics 19:477-88. 2009
  6. doi Colon tumour cells increase PGE(2) by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation
    Heather R Roberts
    School of Cellular and Molecular Medicine, Cancer Research UK Colorectal Tumour Biology Research Group, University of Bristol, Bristol, BS8 1TD, UK
    Carcinogenesis 32:1741-7. 2011
  7. ncbi Transactivation activity of human papillomavirus type 16 E6*I on aldo-keto reductase genes enhances chemoresistance in cervical cancer cells
    Panata Wanichwatanadecha
    Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand
    J Gen Virol 93:1081-92. 2012
  8. ncbi Aberrant pre-receptor regulation of estrogen and progesterone action in endometrial cancer
    Tina Smuc
    Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 301:74-82. 2009
  9. doi Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer
    Johannes Hofland
    Departments of Internal Medicine, Urology, and Pathology, Erasmus MC, P O Box 2040, 3000 CA Rotterdam, The Netherlands
    Cancer Res 70:1256-64. 2010
  10. ncbi cDNA cloning, expression and characterization of human prostaglandin F synthase
    T Suzuki-Yamamoto
    Department of Anatomy and Cell Biology, School of Medicine, The University of Tokushima, Kuramoto, Japan
    FEBS Lett 462:335-40. 1999

Detail Information

Publications187 found, 100 shown here

  1. ncbi Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer
    Michael Stanbrough
    Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cancer Res 66:2815-25. 2006
    ..These results indicate that enhanced intracellular conversion of adrenal androgens to testosterone and dihydrotestosterone is a mechanism by which prostate cancer cells adapt to androgen deprivation and suggest new therapeutic targets...
  2. pmc Inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3): overview and structural insights
    Michael C Byrns
    Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, 130C John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, United States
    J Steroid Biochem Mol Biol 125:95-104. 2011
    ..These pockets can be used to further improve the binding affinity and selectivity of the currently available AKR1C3 inhibitors. Article from the special issue on Targeted Inhibitors...
  3. ncbi Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity
    K Matsuura
    Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, 502 8585, Japan
    J Biochem 124:940-6. 1998
    ..These results suggest that AKR1C3 acts as prostaglandin D2 11-ketoreductase, and that its principal gene in the human has a coding region represented by DBDH cDNA...
  4. doi β-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells
    Helena J M Smartt
    Cancer Research UK Colorectal Tumour Biology Research Group, School of Cellular and Molecular Medicine, University Walk, University of Bristol, Bristol, UK
    Gut 61:1306-14. 2012
    ..As Wnt/β-catenin signalling is also deregulated early in colorectal neoplasia, a study was undertaken to determine whether β-catenin represses 15-PGDH expression...
  5. doi Induction of 1C aldoketoreductases and other drug dose-dependent genes upon acquisition of anthracycline resistance
    Zachary W Veitch
    Department of Biology, Laurentian University, Northern Ontario School of Medicine, Sudbury, Canada
    Pharmacogenet Genomics 19:477-88. 2009
    ....
  6. doi Colon tumour cells increase PGE(2) by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation
    Heather R Roberts
    School of Cellular and Molecular Medicine, Cancer Research UK Colorectal Tumour Biology Research Group, University of Bristol, Bristol, BS8 1TD, UK
    Carcinogenesis 32:1741-7. 2011
    ....
  7. ncbi Transactivation activity of human papillomavirus type 16 E6*I on aldo-keto reductase genes enhances chemoresistance in cervical cancer cells
    Panata Wanichwatanadecha
    Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand
    J Gen Virol 93:1081-92. 2012
    ..Taken together, it was concluded that 16E6*I has a novel function in upregulating expression of AKR1C and, in concert with E7, has implications for drug treatment in HPV-mediated cervical cancer...
  8. ncbi Aberrant pre-receptor regulation of estrogen and progesterone action in endometrial cancer
    Tina Smuc
    Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 301:74-82. 2009
    ..Up-regulation of AKR1C1 and AKR1C3 can result in lower levels of the protective progesterone, which acts mainly via PR-B...
  9. doi Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer
    Johannes Hofland
    Departments of Internal Medicine, Urology, and Pathology, Erasmus MC, P O Box 2040, 3000 CA Rotterdam, The Netherlands
    Cancer Res 70:1256-64. 2010
    ....
  10. ncbi cDNA cloning, expression and characterization of human prostaglandin F synthase
    T Suzuki-Yamamoto
    Department of Anatomy and Cell Biology, School of Medicine, The University of Tokushima, Kuramoto, Japan
    FEBS Lett 462:335-40. 1999
    ..These results support the notion that human PGFS plays an important role in the pathogenesis of allergic diseases such as asthma...
  11. ncbi Tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily
    Stephan Steckelbroeck
    Department of Pharmacology, University of Pennsylvania School of Medicine, 130C John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    J Pharmacol Exp Ther 316:1300-9. 2006
    ..The low hepatic formation of 3alpha-hydroxytibolone suggests that AKR1C4 is not the primary source of this metabolite and instead it maybe formed by an intestinal or enterobacterial 3alpha-HSD...
  12. pmc Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N-phenyl-aminobenzoates and their structure-activity relationships
    Adegoke O Adeniji
    Department of Pharmacology and Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Med Chem 55:2311-23. 2012
    ..Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC...
  13. ncbi Deoxycorticosterone inactivation by AKR1C3 in human mineralocorticoid target tissues
    Kamalesh K Sharma
    Department of Obstetrics Gynecology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell Endocrinol 248:79-86. 2006
    ..Our findings suggest that AKR1C3 protects the mineralocorticoid receptor from activation by DOC in mineralocorticoid target cells of the kidney and colon, analogous to cortisol inactivation by 11beta-hydroxysteroid dehydrogenase type 2...
  14. ncbi Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3
    Romana Novotna
    Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, CZ 50005 Hradec Kralove, Czech Republic
    Toxicol Lett 181:1-6. 2008
    ....
  15. doi Prostaglandin F(2alpha) suppresses early phase of adipogenesis, but is not associated with osteoblastogenesis in mouse mesenchymal stem cells
    Ko Fujimori
    Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4 20 1 Nasahara, Takatsuki, Osaka 569 1094, Japan
    Prostaglandins Other Lipid Mediat 93:52-9. 2010
    ..Therefore, PGF(2alpha) suppressed the progression of early phase adipogenesis after determination of the cell fate that causes MSC to differentiate into adipocytes...
  16. pmc Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3)
    Adegoke O Adeniji
    Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 6084, USA
    Bioorg Med Chem Lett 21:1464-8. 2011
    ..These compounds may be useful in treatment and/or prevention of CRPC as well as understanding the role of AKR1C3 in endocrinology...
  17. pmc Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia
    Farhat L Khanim
    School of Biosciences, University of Birmingham, Birmingham, United Kingdom
    PLoS ONE 4:e8147. 2009
    ..In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis...
  18. pmc Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid hormone and prostaglandin metabolism that may explain its over-expression in breast cancer
    Michael C Byrns
    Centers of Excellence in Environmental Toxicology and Cancer Pharmacology, Department of Pharmacology, University of Pennsylvania School of Medicine, 130C John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, United States
    J Steroid Biochem Mol Biol 118:177-87. 2010
    ....
  19. pmc Suppression of adipocyte differentiation by aldo-keto reductase 1B3 acting as prostaglandin F2alpha synthase
    Ko Fujimori
    Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4 20 1 Nasahara, Takatsuki, Osaka 569 1094, Japan
    J Biol Chem 285:8880-6. 2010
    ..These results indicate that AKR1B3 acts as the PGFS in adipocytes and that AKR1B3-produced PGF(2alpha) suppressed adipocyte differentiation by acting through FP receptors...
  20. ncbi Characterization of a monoclonal antibody for human aldo-keto reductase AKR1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase); immunohistochemical detection in breast and prostate
    Hsueh Kung Lin
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19018, USA
    Steroids 69:795-801. 2004
    ..The reagent thus has utility to access the localized expression of AKR1C3 in hormonal dependent malignancies of the breast and prostate...
  21. ncbi Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost
    Junichi Komoto
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045 7534, USA
    Biochemistry 45:1987-96. 2006
    ..Formation of PGF(2)(alpha) from PGH(2) most likely involves a direct hydride transfer from the bound NADPH to the endoperoxide of PGH(2) without the participation of specific amino acid residues...
  22. pmc Suppressed expression of type 2 3alpha/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) in endometrial hyperplasia and carcinoma
    Vladislav Zakharov
    Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Int J Clin Exp Pathol 3:608-17. 2010
    ..However, reduced AKR1C3 expression cannot distinguish hyperplastic endometrium from endometrial adenocarcinoma of endometrial type. The biologic and pathological roles of AKR1C3 in endometrial epithelium require further investigation...
  23. ncbi Crystal structure of human prostaglandin F synthase (AKR1C3)
    Junichi Komoto
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045 7534, USA
    Biochemistry 43:2188-98. 2004
    ..Since the substrate binding cavity of PGFS is relatively large in comparison with those of AKR1C1 and AKR1C2, PGFS (AKR1C3) could catalyze the reduction and/or oxidation reactions of various compounds over a relatively wide pH range...
  24. pmc Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis
    James J Lee
    Gastroenterology Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Carcinogenesis 31:427-34. 2010
    ..Thus, PTGES is a novel HIF-1alpha target gene, involved in prostaglandin E biosynthesis in the esophageal tumor hypoxic microenvironment, and this has implications in diverse tumors types, especially of squamous origin...
  25. pmc 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis
    Seung Jae Myung
    Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 103:12098-102. 2006
    ....
  26. ncbi Reduction of doxorubicin and oracin and induction of carbonyl reductase in human breast carcinoma MCF-7 cells
    Martina Gavelová
    Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, CZ 500 05 Hradec Kralove, Czech Republic
    Chem Biol Interact 176:9-18. 2008
    ..Taken together, the present results seem to suggest that the accelerated metabolic deactivation of ORC or DOX might contribute to the survival of breast cancer cells during exposure to these cytostatics...
  27. ncbi Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase
    Virginie Quidville
    Institut National de la Santé et de la Recherche Médicale Unité 349, Hopital Lariboisiere, Centre Viggo Petersen, 2 rue Ambroise Pare, 75475 Paris Cedex 10, France
    Endocrinology 145:2561-71. 2004
    ..The synthesis enzyme, COX-1, and the catabolism enzyme 15-prostaglandin dehydrogenase, could be involved in MTC development...
  28. doi AKR1C3 as a potential target for the inhibitory effect of dietary flavonoids
    Lucie Skarydová
    Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic
    Chem Biol Interact 178:138-44. 2009
    ..Moreover, since the inhibition is selective towards AKR1C3, 2'-hydroxyflavanone could be useful for treating or preventing hormone-dependent malignancies like prostate and breast cancer...
  29. doi Prostaglandin catabolic enzymes as tumor suppressors
    Hsin Hsiung Tai
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Cancer Metastasis Rev 30:409-17. 2011
    ..Future directions of research on these prostaglandin catabolic enzymes as tumor suppressors are also discussed...
  30. doi Prostaglandin expression profile in hypoxic osteoblastic cells
    Christina M Lee
    Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, 1321 Haring Hall, One Shields Ave, Davis, CA 95616, USA
    J Bone Miner Metab 28:8-16. 2010
    ..Previous studies have detected release of prostaglandins from areas of damaged bone, such as a fracture site, and our data may contribute to an understanding of how this release is regulated...
  31. pmc N-Benzoyl anthranilic acid derivatives as selective inhibitors of aldo-keto reductase AKR1C3
    Maša Sinreih
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
    Bioorg Med Chem Lett 22:5948-51. 2012
    ..In addition, five selective inhibitors of AKR1C3 were identified. The most promising inhibitors were compounds 10 and 13, with IC(50) values of 0.31 μM and 0.35 μM for AKR1C3, respectively...
  32. ncbi 15-Hydroxyprostaglandin dehydrogenase can be induced by dexamethasone and other glucocorticoids at the therapeutic level in A549 human lung adenocarcinoma cells
    Min Tong
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Arch Biochem Biophys 435:50-5. 2005
    ..The induction of 15-PGDH expression by dexamethasone and other glucocorticoids at the therapeutic level provides an additional biochemical mechanism for the anti-inflammatory action of these glucocorticoids...
  33. ncbi Genomic structure and transcriptional regulation of the human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase gene
    A Nandy
    IHF Institute for Hormone and Fertility Research, University of Hamburg, Falkenried 88, 20251 Hamburg, Germany
    J Mol Endocrinol 31:105-21. 2003
    ..CREB activated the PGDH-DE construct through the CREB1 site. These results defined the distal element as an integrator of transcriptional regulation by AP-1, Ets and CREB proteins...
  34. ncbi Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival
    YARI E MARIN
    The Johnson and Johnson Skin Research Center, CPPW, a Unit of Johnson and Johnson Consumer Companies Inc, Skillman, NJ 08558, USA
    Exp Dermatol 18:611-8. 2009
    ....
  35. ncbi Synergistic induction of the nicotinamide adenine dinucleotide-linked 15-hydroxyprostaglandin dehydrogenase by an androgen and interleukin-6 or forskolin in human prostate cancer cells
    Min Tong
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536 0082, USA
    Endocrinology 145:2141-7. 2004
    ..These results indicate that the induction of 15-PGDH by DHT, IL-6, and forskolin in LNCaP cells may involve a functional androgen receptor and phosphorylation-dependent multiple signaling pathways...
  36. pmc Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by virtual screening of a fragment library
    Petra Brozic
    Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    J Med Chem 55:7417-24. 2012
    ..Two of the best selective AKR1C3 inhibitors had K(i) values of 0.1 and 2.7 μM, exceeding expected activity for fragments. The compounds identified represent an excellent starting point for further hit-to-lead development...
  37. ncbi Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by PMA
    M Frenkian
    INSERM Unit 349, Centre Viggo Petersen, , , Paris Cedex 10, 75475, France
    Prostaglandins Leukot Essent Fatty Acids 64:87-93. 2001
    ..Indomethacin, in association with PMA can consequently exert a dual control on key enzymes of PGE2 metabolism without modifying adhesion of the cells...
  38. ncbi Mechanical stress and prostaglandin E2 synthesis in cartilage
    Marjolaine Gosset
    Physiology and Physiopathology Laboratory, Paris Universitas UPMC Paris VI and CNRS UMR 7079, 75252 Paris, Cedex 5, France
    Biorheology 45:301-20. 2008
    ..Notably, compression increases mPGES-1 mRNA and protein expression in cartilage explants. Thus, the mechanosensitive mPGES-1 enzyme represents a potential therapeutic target in osteoarthritis...
  39. pmc Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3
    Jack U Flanagan
    Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand
    PLoS ONE 7:e43965. 2012
    ..This new data from ten crystal structures greatly broadens the base of structures available for future structure-guided drug discovery efforts...
  40. doi 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: highly potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase AKR1C3
    Stephen M F Jamieson
    Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
    J Med Chem 55:7746-58. 2012
    ....
  41. doi Selective inhibition of human type-5 17β-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis
    Satoshi Endo
    Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu 501 1196, Japan
    J Nat Prod 75:716-21. 2012
    ..Additionally, 1 suppressed the proliferation of PC3 prostatic cancer cells stimulated by AKR1C3 overexpression. This study is the first demonstration that 1 is a highly selective inhibitor of AKR1C3...
  42. pmc 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer
    Hsin Hsiung Tai
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Prostaglandins Other Lipid Mediat 83:203-8. 2007
    ..These results suggest that tumor suppressive action of these agents may, in part, be related to their ability to induce 15-PGDH expression...
  43. pmc Overexpression of aldo-keto reductase 1C3 (AKR1C3) in LNCaP cells diverts androgen metabolism towards testosterone resulting in resistance to the 5α-reductase inhibitor finasteride
    Michael C Byrns
    Center of Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
    J Steroid Biochem Mol Biol 130:7-15. 2012
    ..Treatment options in prostate cancer that target 5α-reductase where AKR1C3 co-exists may be less effective due to the diversion of Δ(4)-Adione to testosterone...
  44. ncbi Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer
    K Wako
    Division of Urology, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    J Clin Pathol 61:448-54. 2008
    ..The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined...
  45. ncbi Prostaglandin F synthase
    Kikuko Watanabe
    Division of Applied Life Sciences, Graduate School of Integrated Sciences and Arts, University of East Asia, Shimonoseki, Yamaguchi, Japan
    Prostaglandins Other Lipid Mediat 68:401-7. 2002
    ..Here, these three pathways of PGF synthesis by these enzymes are reviewed, and the physiological roles of the enzymes are discussed...
  46. pmc 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer
    Michael G Backlund
    Department of Medicine, Cell and Developmental Biology, Vanderbilt University Medical Center and the Vanderbilt Ingram Cancer Center, Nashville, Tennessee 37232 6838, USA
    J Biol Chem 280:3217-23. 2005
    ..In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression...
  47. ncbi 15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human breast cancer
    Ido Wolf
    Division of Hematology Oncology, Cedars Sinai Medical Center, University of California at Los Angeles School of Medicine, Los Angeles, CA 90048, USA
    Cancer Res 66:7818-23. 2006
    ..Our results indicate for the first time that 15-PGDH may be a novel tumor suppressor gene in breast cancer, and suggest that this enzyme can modulate the ER pathway...
  48. ncbi Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma
    K M Fung
    Department of Urology, University of Oklahoma Health Sciences Center, 920 Stanton L Young Blvd, WP3150, Oklahoma City, OK 73104, USA
    Endocr Relat Cancer 13:169-80. 2006
    ..Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells...
  49. ncbi AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer
    Tea Lanisnik Rizner
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 248:126-35. 2006
    ..It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2...
  50. ncbi Reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase expression in A549 human lung adenocarcinoma cells
    Min Tong
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky Lexington, KY 40536 0082, USA
    Carcinogenesis 27:2170-9. 2006
    ..The levels of IL-1beta-induced COX-2 expression appeared to correlate inversely with those of 15-PGDH expression in the cells. These results support the contention that COX-2 and 15-PGDH are regulated reciprocally in A549 cells...
  51. ncbi NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer
    Yunfei Ding
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA
    Carcinogenesis 26:65-72. 2005
    ..Furthermore, the expression of 15-PGDH was found to be stimulated by hyaluronidase. These results suggest that 15-PGDH may decrease the level of proliferative PGE2, induce apoptosis and function like a tumor suppressor...
  52. ncbi The aldo-keto reductase AKR1C3 contributes to 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol mediated oxidative DNA damage in myeloid cells: implications for leukemogenesis
    Jane Birtwistle
    School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Mutat Res 662:67-74. 2009
    ....
  53. ncbi 15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary thyroid carcinoma cell line
    Virginie Quidville
    Institut National de la Santé et de la Recherche Médicale U 606, Paris 75010, France
    Prostaglandins Other Lipid Mediat 81:14-30. 2006
    ..NSAIDs defined by their COX inhibition should also be defined by their effect on 15-PGDH...
  54. doi The effect of ovarian steroids on oxytocin-stimulated secretion and synthesis of prostaglandins in bovine myometrial cells
    Dominika Slonina
    Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10 747 Olsztyn, Poland
    Prostaglandins Other Lipid Mediat 90:69-75. 2009
    ....
  55. doi 15-prostaglandin dehydrogenase expression alone or in combination with ACSM1 defines a subgroup of the apocrine molecular subtype of breast carcinoma
    Julio E Celis
    Department of Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Mol Cell Proteomics 7:1795-809. 2008
    ....
  56. ncbi Cytokeratin 20, AN43, PGDH, and COX-2 expression in transitional and squamous cell carcinoma of the bladder
    Jason R Gee
    Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Urol Oncol 21:266-70. 2003
    ..CK20, AN43 and PGDH decreased but COX-2 expression increased in higher stage tumors. The histologic phenotype of these cancers is reflected in their expression of these proteins and is modified further as tumors progress in stage...
  57. pmc Tissue distribution of human AKR1C3 and rat homolog in the adult genitourinary system
    Joseph Azzarello
    Department of Urology, University of Oklahoma Health Sciences Center, 800 Research Parkway, Room 462, Oklahoma City, OK 73034, USA
    J Histochem Cytochem 56:853-61. 2008
    ..These features warrant future studies of AKR1C3 in both hormone- and non-hormone-associated tissues and identification of the rodent homolog for establishing animal models...
  58. ncbi AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells
    Shaobin Wang
    Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States
    Mol Cell Endocrinol 289:60-6. 2008
    ..Our results suggested that both AKR1C2 and AKR1C3 mediate similar PGD2 conversion toward the accumulation of proliferative signals through FP and PI3K/Akt signaling pathways to promote prostate cell proliferation...
  59. pmc 15-Hydroxyprostaglandin dehydrogenase, a COX-2 oncogene antagonist, is a TGF-beta-induced suppressor of human gastrointestinal cancers
    Min Yan
    Department of Medicine, Case Western Reserve University and University Hospitals, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 101:17468-73. 2004
    ..These findings thus delineate an enzymatic pathway that induces colon cancer suppression, a pathway that is activated by TGF-beta and mediated by 15-PGDH...
  60. ncbi Key NAD+-binding residues in human 15-hydroxyprostaglandin dehydrogenase
    Hoon Cho
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Arch Biochem Biophys 433:447-53. 2005
    ..These results suggest that Ile-17, Asn-91, and Val-186 are involved in the interaction with NAD(+) and contribute to the full catalytic activity of 15-PGDH...
  61. ncbi Cloning and sequence analysis of the cDNA for human placental NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase
    C M Ensor
    Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536 0082
    J Biol Chem 265:14888-91. 1990
    ..4 kilobases and the other of 2.0 kilobases. Isolation of the cDNA for 15-hydroxyprostaglandin dehydrogenase should facilitate studies on the structure, function, and regulation of this enzyme...
  62. ncbi C-Terminal region of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase is involved in the interaction with prostaglandin substrates
    H Zhou
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Eur J Biochem 268:3368-74. 2001
    ..The C-terminal region appears to be more important for the interaction of the enzyme with the prostaglandin substrates than with the coenzyme...
  63. ncbi Thiazolidinediones as a novel class of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors
    Hoon Cho
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Arch Biochem Biophys 405:247-51. 2002
    ..This regulatory site appears to overlap with the activator site occupied by imipramine since activation of the enzyme by this activator is competitively inhibited by compound CT-8...
  64. ncbi Expression of 15-hydroxyprostaglandin dehydrogenase, a COX-2 antagonist and tumour suppressor, is not altered in gastric carcinomas
    Nam Jin Yoo
    Pathology 39:174-5. 2007
  65. pmc Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma
    Michael J Lewis
    Department of Biology University of Western Ontario, London, Canada
    BMC Cancer 4:27. 2004
    ..The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression...
  66. ncbi Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5
    S X Lin
    Molecular Endocrinology Research Center at Laval University Hospital Research Center CHUL, CHUQ, Laval University, Que, Canada G1V 4G2
    Mol Cell Endocrinol 248:38-46. 2006
    ..The multi-specificity contributes significantly to steroid metabolism in peripheral tissues, due to the high levels of 17beta-HSD5 mRNA in both breast and prostate tissues...
  67. ncbi Inhibition of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) by cyclooxygenase inhibitors and chemopreventive agents
    H Cho
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 0082, USA
    Prostaglandins Leukot Essent Fatty Acids 67:461-5. 2002
    ..Among these compounds, ciglitazone appeared to be the most powerful inhibitor (IC(50)=2.7 microM). Inhibition by ciglitazone was non-competitive with respect to NAD(+) and uncompetitive with respect to PGE(2)...
  68. ncbi Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin
    Andrew L Lovering
    The School of Biosciences, The University of Birmingham, Birmingham, United Kingdom
    Cancer Res 64:1802-10. 2004
    ..The data underline AKR1C3 as a COX-independent target for NSAID and will provide a structural basis for the future development of new cancer therapies with reduced COX-dependent side effects...
  69. ncbi Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family
    M Krook
    Department of Chemistry I, Karolinska Institutet, Stockholm, Sweden
    Biochemistry 29:738-43. 1990
    ..The protein has four cysteine residues (five with the positional microheterogeneity), but there is no evidence for functional importance of any of these residues.(ABSTRACT TRUNCATED AT 250 WORDS)..
  70. ncbi Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression
    Jason R Mann
    Departments of Cell and Developmental Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, 2300 Pierce Avenue, Nashville, TN 37232, USA
    Cancer Res 66:6649-56. 2006
    ..These data indicate that PGDH may serve a tumor suppressor function in colorectal cancer and provide a possible COX-2-independent way to target PGE(2) to inhibit cancer progression...
  71. ncbi Inhibition of epidermal growth factor receptor signaling elevates 15-hydroxyprostaglandin dehydrogenase in non-small-cell lung cancer
    Li Yang
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Cancer Res 67:5587-93. 2007
    ..This effect is reversible in a subset of NSCLC upon treatment with an EGFR TKI...
  72. ncbi Levels of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-alpha
    Taisuke Otani
    Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA
    Am J Physiol Gastrointest Liver Physiol 290:G361-8. 2006
    ..The decrease in amounts of 15-PGDH in inflamed mucosa can be explained at least, in part, by TNF-alpha-mediated suppression of 15-PGDH transcription...
  73. ncbi Cytokine-induced coordinate expression of enzymes of prostaglandin biosynthesis and metabolism: 15-hydroxyprostaglandin dehydrogenase
    M D Mitchell
    Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand
    Prostaglandins Leukot Essent Fatty Acids 62:1-5. 2000
    ....
  74. ncbi Prostaglandin catabolizing enzymes
    Hsin Hsiung Tai
    Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington 40536 0082, USA
    Prostaglandins Other Lipid Mediat 68:483-93. 2002
    ..Future investigation may shed more light on the roles of these enzymes in health and diseases...
  75. ncbi The human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase gene promoter is controlled by Ets and activating protein-1 transcription factors and progesterone
    K J Greenland
    IHF Institute for Hormone and Fertility Research, University of Hamburg, Germany
    Endocrinology 141:581-97. 2000
    ....
  76. ncbi Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase
    J E Pawlowski
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104 6084
    J Biol Chem 266:8820-5. 1991
    ..M., Abrams, W. R., and Pawlowski, J. E. (1991) J. Biol. Chem. 266, 8826-8834]. The sequence data presented suggests that 3 alpha-HSD, prostaglandin F synthase, and aldehyde/aldose reductases are members of a common gene family...
  77. ncbi Spermatozoa stimulate prostaglandin synthesis and secretion in bovine oviductal epithelial cells
    Suranga P Kodithuwakku
    Department of Animal Science, University of Peradeniya, Peradeniya 20400, Sri Lanka
    Reproduction 133:1087-94. 2007
    ..Thus, spermatozoa may bear a role in accelerating their own transport into the fertilization site...
  78. ncbi Regulation of the prostaglandin enzymatic system by estradiol and progesterone in nonpregnant sheep cervix
    Qi Zhang
    Department of Obstetrics and Gynecology and the Center of Research for Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Reproduction 133:1027-34. 2007
    ..The expression of COX2, PTGFS, and mPTGES1 mRNA and/or protein was confined in the cervical glandular epithelial cells of nonpregnant sheep...
  79. ncbi Intraluteal regulation of prostaglandin F2 alpha-induced prostaglandin biosynthesis in pseudopregnant rabbits
    M Zerani
    Dipartimento di Biologia Molecolare, Cellulare e Animale, Universita di Camerino, via F Camerini 1, Camerino, Italy
    Reproduction 133:1005-16. 2007
    ....
  80. ncbi Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation
    E Schoof
    Department of Pediatrics, University of Erlangen-Nuremberg, Germany
    Eur J Endocrinol 145:187-92. 2001
    ..11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins...
  81. ncbi Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase
    C E Conner
    Department of Obstetrics and Gynaecology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
    Histochem Cell Biol 116:313-9. 2001
    ....
  82. ncbi Metabolism of PGE2 by prostaglandin dehydrogenase is essential for remodeling the ductus arteriosus
    Kenneth G Coggins
    Department of Medicine, University of North Carolina, Chapel Hill, USA
    Nat Med 8:91-2. 2002
  83. ncbi Coordinate regulation of prostaglandin metabolism for induction of parturition in mice
    Sandra K Winchester
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Endocrinology 143:2593-8. 2002
    ....
  84. pmc A key role for old yellow enzyme in the metabolism of drugs by Trypanosoma cruzi
    Bruno Kilunga Kubata
    Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565 0874, Japan
    J Exp Med 196:1241-51. 2002
    ....
  85. ncbi Expression of key prostaglandin synthases in equine endometrium during late diestrus and early pregnancy
    Derek Boerboom
    Centre de Recherche en Reproduction Animale, Faculte de Medecine, Universite de Montreal, Canada
    Biol Reprod 70:391-9. 2004
    ....
  86. ncbi Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity
    Deborah J Wake
    Endocrinology Unit, Centre for Cardiovascular Science, Queen s Medical Research Institute, University of Edinburgh, Scotland, UK
    Clin Endocrinol (Oxf) 66:440-6. 2007
    ..We aimed to test associations between body fat or fat distribution and mRNA transcript levels for androgen and oestrogen receptors and for enzymes metabolizing sex steroids in adipose tissue...
  87. ncbi Prostaglandin metabolism in human hair follicle
    Laurent Colombe
    Centre Charles Zviak, L Oreal Recherche, 90 rue du General Roguet, Clichy Cedex, France
    Exp Dermatol 16:762-9. 2007
    ..All these observations support the concept that prostaglandins might be involved in hair growth and differentiation control...
  88. pmc Ciglitazone mediates COX-2 dependent suppression of PGE2 in human non-small cell lung cancer cells
    Saswati Hazra
    Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
    Prostaglandins Leukot Essent Fatty Acids 77:51-8. 2007
    ..Here, we report that ciglitazone downregulates PGE2 in NSCLC cells...
  89. ncbi Differential expression of prostaglandin (PG) synthesis enzymes in conceptus during peri-implantation period and endometrial expression of carbonyl reductase/PG 9-ketoreductase in the pig
    Agnieszka Waclawik
    Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Tuwima 10, 10 747 Olsztyn, Poland
    J Endocrinol 194:499-510. 2007
    ..Moreover, high expression of conceptus PGHS-1, mPGES-1, PGFS, and CBR1 after initiation of implantation suggests their significant role in placentation...
  90. ncbi Characterization of prostaglandin F2 alpha production in pregnant and cycling mice
    S Unezaki
    Department of Medical Chemistry, Kansai Medical University, Moriguchi, Japan
    Biol Reprod 55:889-94. 1996
    ..These results suggest that PGF2 alpha production may increase at term and change during the estrous cycle and is associated with an increase in uterine PGF synthase concentrations...
  91. ncbi Cloning of guinea pig cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase complementary deoxyribonucleic acids: steroid-modulated gene expression correlates to prostaglandin F2 alpha secretion in cultured endometrial cells
    K E Bracken
    Institute for Hormone and Fertility Research, University of Hamburg, Germany
    Endocrinology 138:237-47. 1997
    ..Our findings suggest a differential role for uterine stroma and epithelium in vivo whereby the former acts to remove (via PGDH), and the latter to produce (via COX-2) biologically active prostaglandin...
  92. ncbi Steroid regulation of prostaglandin dehydrogenase activity and expression in human term placenta and chorio-decidua in relation to labor
    F A Patel
    Department of Physiology, University of Toronto, Ontario, Canada
    J Clin Endocrinol Metab 84:291-9. 1999
    ..We conclude that cortisol inhibits PGDH activity and expression and that progestagens increase PGDH activity in human chorion and placenta...
  93. ncbi Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes
    M Nishizawa
    Department of Medical Chemistry Department of Obstetrics and Gynecology, Kansai Medical University, 10 15 Fumizono, Moriguchi, Osaka 570 8506, Japan
    Genes Cells 5:111-25. 2000
    ..High homology between human 20alpha-HSD [AKR 1C1] cDNA with other AKRs had caused difficulty in gene isolation and expression analysis. Thus, the metabolism of progesterone in the human reproductive system remained unclear...
  94. pmc Episode-specific differential gene expression of peripheral blood mononuclear cells in rapid cycling supports novel treatment approaches
    Martin Begemann
    Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Gottingen, Germany
    Mol Med 14:546-52. 2008
    ..This case suggests that rapid cycling is a systemic disease, resembling hibernation, with prostaglandins playing a mediator role...
  95. ncbi Differential production of prostaglandin E(2) in male and female mice subjected to thermal injury contributes to the gender difference in immune function: possible role for 15-hydroxyprostaglandin dehydrogenase
    M S Gregory
    Department of Cell Biology, Neurobiology, and Anatomy, Burn and Shock Institute, Maywood, Illinois 60153, USA
    Cell Immunol 205:94-102. 2000
    ..These data demonstrate that PGE(2) is a critical mediator of immunosuppression in thermally injured female mice and that the increase in circulating PGE(2) is derived, in part, from decreased degradation and clearance of PGE(2)...
  96. pmc Estrogen and progesterone metabolism in the cervix during pregnancy and parturition
    Stefan Andersson
    Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9032, USA
    J Clin Endocrinol Metab 93:2366-74. 2008
    ..Mice deficient in 5alpha-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood...
  97. ncbi Prostaglandin E2 protects lower airways against bronchoconstriction
    John M Hartney
    Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
    Am J Physiol Lung Cell Mol Physiol 290:L105-13. 2006
    ..Thus, whereas compromise of the Ptges/PGE2/Ptger2 pathway does not alter airway responsiveness, genetic modulation that elevates PGE2 levels in the lung attenuates airway responsiveness...
  98. pmc Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders
    Prerna Rastogi
    Department of Pathology, Saint Louis University School of Medicine, Doisy Research Bldg, 3rd Floor, 1110 S Grand Blvd, St Louis, MO 63104, USA
    Am J Physiol Renal Physiol 294:F1129-35. 2008
    ..Since PGE(2) is a cytoprotective eicosanoid, the failure to produce this metabolite in cells isolated from the IC bladder may represent an increased susceptibility to damage by proinfammatory stimuli...
  99. doi Opposite effect of phorbol ester PMA on PTGS2 and PGDH mRNA expression in human chorion trophoblast cells
    Valentina Casciani
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Reprod Sci 15:40-50. 2008
    ..The authors conclude that upon stimulation with the same upstream signals, different downstream intracellular pathways regulate PTGS2 and PGDH mRNA expression...
  100. ncbi Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in vitro and in vivo
    K R Kozak
    Department of Biochemistry and Chemistry, Vanderbilt-Ingram Cancer Center and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 276:36993-8. 2001
    ..Furthermore, these results suggest that the rat is not an adequate model for investigating the biological activities of 2-arachidonylglycerol or glyceryl prostaglandins in humans...
  101. ncbi Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1
    Petra Brozic
    Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
    Mol Cell Endocrinol 259:30-42. 2006
    ..Docking of the flavones in the active site of AKR1C1 revealed their possible binding modes, in which they are sandwiched between the Leu308 and Trp227 of AKR1C1...

Research Grants88

  1. STRUCTURE/FUNCTION OF 3A-HYDROXYSTEROID DEHYDROGENASE
    TREVOR PENNING; Fiscal Year: 2002
    ....
  2. INHIBITION OF 3A HSD BY ANTI-INFLAMMATORY DRUGS
    TREVOR PENNING; Fiscal Year: 1990
    ..These studies may provide information for a rational approach to the design of superior antiinflammatory drugs...
  3. MECHANISMS FOR CHEMOPREVENTION OF COLORECTAL CANCER
    Michael Backlund; Fiscal Year: 2007
    ..It is becoming increasing apparent that the targeting of a single molecule will not be as effective as is needed to have a significant impact on this disease. [unreadable] [unreadable] [unreadable]..
  4. CHEMISTRY OF FOLATE AND PTERIDINE COENZYMES
    JOHN WHITELEY; Fiscal Year: 2000
    ..coli, purified to homogeneity, and crystallized in its apo- and ATP-bound form. Structural characterization of these complexes may contribute to the understanding of how drug efflux pumps function. ..
  5. CHEMISTRY OF FOLATE AND PTERIDINE COENZYMES
    JOHN WHITELEY; Fiscal Year: 1999
    ..coli, purified to homogeneity, and crystallized in its apo- and ATP-bound form. Structural characterization of these complexes may contribute to the understanding of how drug efflux pumps function. ..
  6. ULTRASTRUCTURE OF THE ANTIHYPERTENSIVE PROSTAGLANDINS
    George DeTitta; Fiscal Year: 1980
    ..In the small molecule studies area we plan to continue to examine the structures of prostacyclin and thromboxane analogs in order to fill out our examination of the whole family of compounds...
  7. Genetic Study of Prostaglandin Synthesis/EGFR and Risk of Colorectal Neoplasia
    Cornelia Ulrich; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  8. Genetic Study of Prostaglandin Synthesis/EGFR and Risk of Colorectal Neoplasia
    Cornelia Ulrich; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  9. Prostaglandin E2 and Regulation of Kidney Function
    Thomas Coffman; Fiscal Year: 2007
    ..To identify the genes in the PGE2 pathway controlling renin expression and release. 2. To define the capacity of mPGE synthases to modulate kidney function. 3. To define the impact of PGE2 metabolism by 15-PGDH on renal functions. ..
  10. Prostaglandin E2 and Regulation of Kidney Function
    Thomas Coffman; Fiscal Year: 2006
    ..To identify the genes in the PGE2 pathway controlling renin expression and release. 2. To define the capacity of mPGE synthases to modulate kidney function. 3. To define the impact of PGE2 metabolism by 15-PGDH on renal functions. ..
  11. Prostaglandin E2 and Regulation of Kidney Function
    Thomas Coffman; Fiscal Year: 2009
    ..To identify the genes in the PGE2 pathway controlling renin expression and release. 2. To define the capacity of mPGE synthases to modulate kidney function. 3. To define the impact of PGE2 metabolism by 15-PGDH on renal functions. ..
  12. Prostaglandin E2 and Regulation of Kidney Function
    Thomas Coffman; Fiscal Year: 2005
    ..To identify the genes in the PGE2 pathway controlling renin expression and release. 2. To define the capacity of mPGE synthases to modulate kidney function. 3. To define the impact of PGE2 metabolism by 15-PGDH on renal functions. ..
  13. ENZYMES IN EICOSANOID METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 2004
    ..Furthermore, the program should uncover novel properties of 5-HEDH and shed some light on the role of this enzyme in the inflammatory and allergic reactions. ..
  14. ENZYMES IN EICOSANOID METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 2002
    ..Furthermore, the program should uncover novel properties of 5-HEDH and shed some light on the role of this enzyme in the inflammatory and allergic reactions. ..
  15. ENZYMES IN EICOSANOID METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 2003
    ..Furthermore, the program should uncover novel properties of 5-HEDH and shed some light on the role of this enzyme in the inflammatory and allergic reactions. ..
  16. STRUCTURE AND FUNCTION OF 15-PROSTAGLANDIN DEHYDROGENASE
    Hsin Hsiung Tai; Fiscal Year: 1992
    ..Finally, we plan to elucidate the molecular basis of defective prostaglandin metabolism in genetic hypertensive rats. The results of this program should aid in understanding the biochemistry, physiology and pathophysiology of the enzyme...
  17. STRUCTURE AND FUNCTION OF 15-PROSTAGLANDIN DEHYDROGENASE
    Hsin Hsiung Tai; Fiscal Year: 1993
    ..Finally, we plan to elucidate the molecular basis of defective prostaglandin metabolism in genetic hypertensive rats. The results of this program should aid in understanding the biochemistry, physiology and pathophysiology of the enzyme...
  18. ENZYMES IN PROSTAGLANDIN METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 1980
    The proposed research project aims at studying four different types of 15-hydroxyprostaglandin dehydrogenases and two types of ketoprostaglandin reductases...
  19. ENZYMES IN PROSTAGLANDIN METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 1999
    ..The results of this research program should provide a molecular basis of our understanding of the regulatory mechanisms and the structural and function of two key catabolic enzymes of prostaglandins. ..
  20. ENZYMES IN PROSTAGLANDIN METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 2000
    ..The results of this research program should provide a molecular basis of our understanding of the regulatory mechanisms and the structural and function of two key catabolic enzymes of prostaglandins. ..
  21. ENZYMES IN EICOSANOID METABOLISM
    Hsin Hsiung Tai; Fiscal Year: 2001
    ..Furthermore, the program should uncover novel properties of 5-HEDH and shed some light on the role of this enzyme in the inflammatory and allergic reactions. ..
  22. Human Aldo Keto Reductases and Steroid Hormone Action
    TREVOR PENNING; Fiscal Year: 2004
    ..These inhibitors may provide tools to dissect function and provide routes to the first Selective Intracrine Modulators that target AKRs. ..
  23. GPX1 ENZYME REGULATION BY OXIDATIVE XENOBIOTICS
    Michael Kelner; Fiscal Year: 1999
    ..These studies will provide critical information regarding cellular response to oxidative stress and aid in determining if a common regulatory mechanism exists for GSH-dependent enzymes. ..
  24. Human aldo-keto reductases and nuclear receptor action
    TREVOR PENNING; Fiscal Year: 2009
    ..Aim 4, will use crystal structures of AKR1C3"NADP(H)"NSAID complexes to develop AKR1C3 isoform specific inhibitors. These studies will establish whether AKR1C3 is a non-Cox target for the cancer chemopreventive roles of NSAIDs. ..
  25. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 2002
    ..Sites of cleavage or base modification will be compared to mutational hot spots observed in human tumors. The transforming potential of BPQ treated ras will be measured by foci formation in NIH/3T3 cells. ..
  26. Halogenated Alkenes and Microsomal GSH-transferases
    Michael Kelner; Fiscal Year: 2008
    ..4] To determine the relative contribution of MGST1 and MGST2 to cellular antioxidant capacity through studies utilizing human MGST1 and MGST2 null cells. ..
  27. INVESTIGATION INTO PARAQUAT CYTOTOXICITY
    Michael Kelner; Fiscal Year: 1990
    ..The mechanism and cellular level (DNA, RNA, protein synthesis) by which this cell continues to express glutathione peroxidase, even when exposed to paraquat, will be determined...
  28. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 2000
    ..Sites of cleavage or base modification will be compared to mutational hot spots observed in human tumors. The transforming potential of BPQ treated ras will be measured by foci formation in NIH/3T3 cells. ..
  29. PROSTAGLANDINS IN PRIMATE OVULATORY FOLLICLES
    DIANE DUFFY; Fiscal Year: 2002
    ..This may provide insight into the mechanisms leading to infertility (e.g., leuteinized unruptured follice syndrome) and support the developoment of PG synthesis inhibitors of PG synthesis inhibitors for use as contraceptives. ..
  30. COX-2 Inhibitors, APC and Colon Cancer Prevention
    Kotha Subbaramaiah; Fiscal Year: 2006
    ..These studies will enhance our understanding of the mechanistic link between COX-2 and colorectal cancer and potentially assist us in optimizing the use of selective COX-2 inhibitors as therapy. ..
  31. Polarization of Dendritic Cells by CD8 T cells
    Pawel Kalinski; Fiscal Year: 2003
    ..abstract_text> ..
  32. Regulation of DC Activity by Memory and Effector CD8+ T Cells
    Pawel Kalinski; Fiscal Year: 2009
    ..abstract_text> ..
  33. Vascular and Inflammatory Predictors of MCI Risk and Progression
    ROSEBUD ROBERTS; Fiscal Year: 2007
    ..The K01 award will culminate in an R01 application that will pave the way for the candidate to become an independent investigator in MCI and AD research. [unreadable] [unreadable] [unreadable]..
  34. Center of Excellence in Environmental Toxicology
    TREVOR PENNING; Fiscal Year: 2008
    ..The COEP has forged relationships with community partners for outreach. The COEP goal will be to reduce the risk of harmful exposures and improve the public health of vulnerable populations within these communities. ..
  35. PROSTAGLANDINS IN PRIMATE OVULATORY FOLLICLES
    DIANE DUFFY; Fiscal Year: 2003
    ..This may provide insight into the mechanisms leading to infertility (e.g., leuteinized unruptured follice syndrome) and support the developoment of PG synthesis inhibitors of PG synthesis inhibitors for use as contraceptives. ..
  36. Aldo-Keto Reductases and PAH Metabolism/Activation
    Trevor M Penning; Fiscal Year: 2010
    ..These studies will inform genotyping and validate genomic studies of cancer of the airway and improve risk assessment prediction. ..
  37. Human aldo-keto reductases and nuclear receptor action
    TREVOR PENNING; Fiscal Year: 2008
    ..Aim 4, will use crystal structures of AKR1C3"NADP(H)"NSAID complexes to develop AKR1C3 isoform specific inhibitors. These studies will establish whether AKR1C3 is a non-Cox target for the cancer chemopreventive roles of NSAIDs. ..
  38. Halogenated Alkenes and Microsomal GSH-transferases
    Michael Kelner; Fiscal Year: 2009
    ..4] To determine the relative contribution of MGST1 and MGST2 to cellular antioxidant capacity through studies utilizing human MGST1 and MGST2 null cells. ..
  39. Pathways of PAH activation in human lung cells
    TREVOR PENNING; Fiscal Year: 2008
    ..These studies will identify major BP-metabolites in NHBE cells which could be used to biomonitor human PAH exposure, and validate candidate genes for genetic predisposition studies. ..
  40. Aldo-Keto Reductases and PAH Metabolism/Activation
    TREVOR PENNING; Fiscal Year: 2009
    ..These studies will inform genotyping and validate genomic studies of cancer of the airway and improve risk assessment prediction. ..
  41. Structure/Function of Steroid Transforming AKR's
    TREVOR PENNING; Fiscal Year: 2008
    ..This application will establish whether these genetic changes result in abnormal bile-acid production and are causal in these deficiencies. ..
  42. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2010
    ..This application will establish whether these genetic changes result in abnormal bile-acid production and are causal in these deficiencies. ..
  43. Aldo-Keto Reductases and PAH Metabolism/Activation
    TREVOR PENNING; Fiscal Year: 2007
    ..Validation of a role for AKRs in PAH-induced lung carcinogenesis may target this pathway for prevention and intervention of this disease. ..
  44. Prostaglandin Receptors in Primate Ovulatory Follicles
    DIANE DUFFY; Fiscal Year: 2007
    ....
  45. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 2004
    ..abstract_text> ..
  46. Human Aldo Keto Reductases and Steroid Hormone Action
    TREVOR PENNING; Fiscal Year: 2003
    ..These inhibitors may provide tools to dissect function and provide routes to the first Selective Intracrine Modulators that target AKRs. ..
  47. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 1993
    ..The second portion of the project will examine the effect of modifying anti-oxidant enzymes, again through introduction of sense or anti-sense expression vectors, on the life span of these fibroblasts...
  48. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM
    TREVOR PENNING; Fiscal Year: 1992
    ..The mRNA species coding for the human enzyme will be identified by Northern analysis using the cDNA for the rat liver enzyme...
  49. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM
    TREVOR PENNING; Fiscal Year: 1991
    ..The mRNA species coding for the human enzyme will be identified by Northern analysis using the cDNA for the rat liver enzyme...
  50. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM
    TREVOR PENNING; Fiscal Year: 1990
    ..The mRNA species coding for the human enzyme will be identified by Northern analysis using the cDNA for the rat liver enzyme...
  51. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 1993
    ..The mutagenicity of these PAH o-quinones will be assessed using Salmonella tester strains (Ta102 and TA104) which are sensitive to mutagens that cause oxidative DNA damage...
  52. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 1999
    ..Sites of cleavage or base modification will be compared to mutational hot spots observed in human tumors. The transforming potential of BPQ treated ras will be measured by foci formation in NIH/3T3 cells. ..
  53. COORDINATE REGULATION OF THE NONCLASSICAL GPX ENZYMES
    Michael Kelner; Fiscal Year: 1999
    ....
  54. COORDINATE REGULATION OF THE NONCLASSICAL GPX ENZYMES
    Michael Kelner; Fiscal Year: 2000
    ....
  55. Human Aldo Keto Reductases and Steroid Hormone Action
    TREVOR PENNING; Fiscal Year: 2002
    ..These inhibitors may provide tools to dissect function and provide routes to the first Selective Intracrine Modulators that target AKRs. ..
  56. GPX1 ENZYME REGULATION BY OXIDATIVE XENOBIOTICS
    Michael Kelner; Fiscal Year: 2002
    ..These studies will provide critical information regarding cellular response to oxidative stress and aid in determining if a common regulatory mechanism exists for GSH-dependent enzymes. ..
  57. Vascular and Inflammatory Predictors of MCI Risk and Progression
    ROSEBUD ROBERTS; Fiscal Year: 2008
    ..The K01 award will culminate in an R01 application that will pave the way for the candidate to become an independent investigator in MCI and AD research. [unreadable] [unreadable] [unreadable]..
  58. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 2002
    ..abstract_text> ..
  59. Symposium on Aldo-Keto Reductases & Toxicant Metabolism
    TREVOR PENNING; Fiscal Year: 2002
    ..abstract_text> ..
  60. Aldo-Keto Reductases and PAH Metabolism/Activation
    TREVOR PENNING; Fiscal Year: 2003
    ..Validation of a role for AKRs in PAH-induced lung carcinogenesis may target this pathway for prevention and intervention of this disease. ..
  61. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 2001
    ..Sites of cleavage or base modification will be compared to mutational hot spots observed in human tumors. The transforming potential of BPQ treated ras will be measured by foci formation in NIH/3T3 cells. ..
  62. Structure/Function of Steroid Hormone Transforming AKRs
    TREVOR PENNING; Fiscal Year: 2003
    ..Completion of these aims will provide structural details of how AKRs transform steroid hormones. ..
  63. Genetic Polymorphisms Benign Prostatic Hyperplasia
    ROSEBUD ROBERTS; Fiscal Year: 2002
    ..This community-based cohort study should provide insights that should improve our understanding of the genetic control of hormonal mechanisms in the pathogenesis of BPH. ..
  64. STRUCTURE/FUNCTION OF 3A-HYDROXYSTEROID DEHYDROGENASE
    TREVOR PENNING; Fiscal Year: 2001
    ....
  65. GPX1 ENZYME REGULATION BY OXIDATIVE XENOBIOTICS
    Michael Kelner; Fiscal Year: 2001
    ..These studies will provide critical information regarding cellular response to oxidative stress and aid in determining if a common regulatory mechanism exists for GSH-dependent enzymes. ..
  66. Human aldo-keto reductases and nuclear receptor action
    TREVOR PENNING; Fiscal Year: 2007
    ..Aim 4, will use crystal structures of AKR1C3"NADP(H)"NSAID complexes to develop AKR1C3 isoform specific inhibitors. These studies will establish whether AKR1C3 is a non-Cox target for the cancer chemopreventive roles of NSAIDs. ..
  67. Structure/Function of Steroid Hormone Transforming AKRs
    TREVOR PENNING; Fiscal Year: 2006
    ..Completion of these aims will provide structural details of how AKRs transform steroid hormones. ..
  68. DIHYDRODIOL DEHYDROGENASE AND PAH METABOLISM/ACTIVATION
    TREVOR PENNING; Fiscal Year: 2000
    ..Sites of cleavage or base modification will be compared to mutational hot spots observed in human tumors. The transforming potential of BPQ treated ras will be measured by foci formation in NIH/3T3 cells. ..
  69. Structure/Function of Steroid Hormone Transforming AKRs
    TREVOR PENNING; Fiscal Year: 2004
    ..Completion of these aims will provide structural details of how AKRs transform steroid hormones. ..
  70. Human Aldo Keto Reductases and Steroid Hormone Action
    TREVOR PENNING; Fiscal Year: 2005
    ..These inhibitors may provide tools to dissect function and provide routes to the first Selective Intracrine Modulators that target AKRs. ..
  71. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 2005
    ..abstract_text> ..
  72. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 1992
    ..The second portion of the project will examine the effect of modifying anti-oxidant enzymes, again through introduction of sense or anti-sense expression vectors, on the life span of these fibroblasts...
  73. Human aldo-keto reductases and nuclear receptor action
    TREVOR PENNING; Fiscal Year: 2009
    ..This proposal is aimed at developing a stable isotope dilution liquid chromatography mass spectrometry method to measure the intraprostatic androgen metabolome which could be used to better diagnose and treat prostate cancer. ..
  74. Structure/Function of Steroid Hormone Transforming AKRs
    TREVOR PENNING; Fiscal Year: 2005
    ..Completion of these aims will provide structural details of how AKRs transform steroid hormones. ..