isoenzymes

Summary

Summary: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics.

Top Publications

  1. pmc ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
    Christophe Ginestier
    Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Cell Stem Cell 1:555-67. 2007
  2. pmc Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis
    Emina H Huang
    Department of Surgery, University of Florida, Gainesville, Florida, USA
    Cancer Res 69:3382-9. 2009
  3. pmc Nitric oxide synthases: structure, function and inhibition
    W K Alderton
    In Vitro Pharmacology Department, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
    Biochem J 357:593-615. 2001
  4. pmc Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer
    Emmanuelle Charafe-Jauffret
    Department of Molecular Oncology, Institut Paoli Calmettes UMR891 Institut National de la Sante et de la Recherche Medicale, Universite de la Mediterranee, Marseille Cancer Research Center, Marseille, France
    Clin Cancer Res 16:45-55. 2010
  5. pmc Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer
    Feng Jiang
    Department of Pathology, Greenbaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201 1192, USA
    Mol Cancer Res 7:330-8. 2009
  6. ncbi Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform
    Paola Marcato
    Departments of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Novia Scotia, Canada
    Cell Cycle 10:1378-84. 2011
  7. ncbi Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance
    Valeria R Fantin
    Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 9:425-34. 2006
  8. pmc Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers
    Shan Deng
    Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e10277. 2010
  9. pmc Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
    Anne Le
    Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:2037-42. 2010
  10. ncbi PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes
    Z Sun
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA
    Nature 404:402-7. 2000

Detail Information

Publications387 found, 100 shown here

  1. pmc ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
    Christophe Ginestier
    Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Cell Stem Cell 1:555-67. 2007
    ..These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts...
  2. pmc Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis
    Emina H Huang
    Department of Surgery, University of Florida, Gainesville, Florida, USA
    Cancer Res 69:3382-9. 2009
    ..These findings also support our original hypothesis, derived previously from mathematical modeling of crypt dynamics, that progressive colonic SC overpopulation occurs during colon tumorigenesis and drives CRC development...
  3. pmc Nitric oxide synthases: structure, function and inhibition
    W K Alderton
    In Vitro Pharmacology Department, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
    Biochem J 357:593-615. 2001
    ..Highly selective inhibitors of iNOS versus eNOS and neuronal NOS have been identified and some of these have potential in the treatment of a range of inflammatory and other conditions in which iNOS has been implicated...
  4. pmc Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer
    Emmanuelle Charafe-Jauffret
    Department of Molecular Oncology, Institut Paoli Calmettes UMR891 Institut National de la Sante et de la Recherche Medicale, Universite de la Mediterranee, Marseille Cancer Research Center, Marseille, France
    Clin Cancer Res 16:45-55. 2010
    ..To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer...
  5. pmc Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer
    Feng Jiang
    Department of Pathology, Greenbaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201 1192, USA
    Mol Cancer Res 7:330-8. 2009
    ..These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer...
  6. ncbi Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform
    Paola Marcato
    Departments of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Novia Scotia, Canada
    Cell Cycle 10:1378-84. 2011
    ..Herein we review the suggested roles of ALDH in CSC biology and the immunohistological studies testing the potential application of ALDH isoforms as novel cancer prognostic indicators...
  7. ncbi Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance
    Valeria R Fantin
    Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 9:425-34. 2006
    ..These results demonstrate that LDH-A plays a key role in tumor maintenance...
  8. pmc Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers
    Shan Deng
    Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e10277. 2010
    ..As a novel cancer stem cell marker, ALDH1 can be used for tumors whose corresponding normal tissues express ALDH1 in relatively restricted or limited levels such as breast, lung, ovarian or colon cancer...
  9. pmc Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
    Anne Le
    Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 107:2037-42. 2010
    ....
  10. ncbi PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes
    Z Sun
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA
    Nature 404:402-7. 2000
    ..signal transduction resulting in cytokine gene expression requires the activation of one or more of the multiple isoenzymes of serine/threonine-specific protein kinase C (PKC)...
  11. ncbi The role of cyclooxygenases in inflammation, cancer, and development
    C S Williams
    Department of Medicine, The Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2279, USA
    Oncogene 18:7908-16. 1999
    ..The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/ or immune function...
  12. ncbi Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers
    Tomonori Tanei
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
    Clin Cancer Res 15:4234-41. 2009
    ..The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers...
  13. pmc ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma
    Michael P Kim
    Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 6:e20636. 2011
    ..Understanding which pancreatic cancer cell populations possess tumor-initiating capabilities is critical to characterizing and understanding the biology of pancreatic CSCs towards therapeutic ends...
  14. ncbi ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome
    Yu Chi Wang
    Laboratory of Epigenetics and Cancer Stem Cells, Tri Service General Hospital, National Defense Medical Center, Taipei, Taiwan
    Am J Pathol 180:1159-69. 2012
    ..The use of a combination of ALDH1 with other stem cell markers may help define ovarian cancer stem cells more stringently...
  15. pmc Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells
    John P Chute
    Division of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:11707-12. 2006
    ..Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs...
  16. pmc Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily
    Satori A Marchitti
    University of Colorado Health Sciences Center, Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, 4200 East Ninth Avenue, C238, Denver, Colorado 80262, USA
    Expert Opin Drug Metab Toxicol 4:697-720. 2008
    ..While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation...
  17. ncbi Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function
    John E Wilson
    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
    J Exp Biol 206:2049-57. 2003
    ..Immunolocalization studies have indicated that, in many cell types, the Type III has a perinuclear localization, the possible metabolic consequences of which remain unclear...
  18. ncbi Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation
    E Hirsch
    Department of Genetics, Biology and Biochemistry, University of Torino, Turin, Italy
    Science 287:1049-53. 2000
    ..These results demonstrate that PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation...
  19. pmc The Akt kinases: isoform specificity in metabolism and cancer
    Eva Gonzalez
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA
    Cell Cycle 8:2502-8. 2009
    ..Here, we summarize recent advances in understanding the roles of Akt isoforms in the regulation of metabolism and cancer, and possible mechanisms contributing to Akt isoform functional specificity...
  20. pmc The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation
    R Ansell
    Department of General and Marine Microbiology, Gothenburg University, Sweden
    EMBO J 16:2179-87. 1997
    The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae...
  21. pmc Protein kinase C theta affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells
    Christa Pfeifhofer
    Institute of Medical Biology and Human Genetics, University of Innsbruck, Schoepfstrasse 41, A 6020 Innsbruck, Austria
    J Exp Med 197:1525-35. 2003
    ..Our finding suggests that PKCtheta plays a critical and nonredundant role in T cell receptor-induced NFAT activation...
  22. ncbi The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42
    G Joberty
    Markey Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908 0577, USA
    Nat Cell Biol 2:531-9. 2000
    ..This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3...
  23. ncbi Structure, function, and control of phosphoinositide-specific phospholipase C
    M J Rebecchi
    Departments of Anesthesiology and Physiology and Biophysics, School of Medicine, State University of New York, Stony Brook, New York 11794, USA
    Physiol Rev 80:1291-335. 2000
    ..In this review we consider each subtype of PLC in organisms ranging from yeast to mammals and discuss their molecular regulation and biological function...
  24. pmc Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer
    So Yeon Park
    Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
    Clin Cancer Res 16:876-87. 2010
    ..To evaluate the expression of stem cell-related markers at the cellular level in human breast tumors of different subtypes and histologic stage...
  25. pmc Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1
    Sarah Ehses
    Institute for Genetics, University of Cologne, Germany
    J Cell Biol 187:1023-36. 2009
    ..we demonstrate that two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities [m-..
  26. ncbi Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1
    J A Le Good
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Science 281:2042-5. 1998
    ..The activation loop phosphorylation of PKCdelta in response to serum stimulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression...
  27. ncbi Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma
    Michael I Koukourakis
    Department of Radiotherapy Oncology, Democritus University of Thrace, PO Box 12, Alexandroupolis 68100, Greece
    Cancer Res 66:632-7. 2006
    ..Tumors survive and grow because they are capable of organizing the regional fibroblasts and endothelial cells into a harmoniously collaborating metabolic domain...
  28. ncbi Determination of the specific substrate sequence motifs of protein kinase C isozymes
    K Nishikawa
    Division of Signal Transduction, Beth Israel Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 272:952-60. 1997
    ..The structural basis for the selectivity of PKC isozymes is discussed based on residues predicted to form the catalytic cleft...
  29. ncbi Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth
    Lei Lv
    Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University, Shanghai 200032, China
    Mol Cell 42:719-30. 2011
    ..These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA...
  30. pmc A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling
    Zachary A Knight
    Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Cell 125:733-47. 2006
    ..These results illustrate systematic target validation using a matrix of inhibitors that span a protein family...
  31. ncbi Essential role of phosphoinositide 3-kinase delta in neutrophil directional movement
    Chanchal Sadhu
    ICOS Corporation, Bothell, WA 98021, USA
    J Immunol 170:2647-54. 2003
    ..These results demonstrate that PI3K delta can play a selective role in the amplification of PIP3 levels that lead to neutrophil polarization and directional migration...
  32. pmc LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer
    Han Xie
    Department of Medicine, Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, and Department of Pathology, Brigham and Women s Hospital, Boston, MA 02215, USA
    Mol Cancer Ther 8:626-35. 2009
    ....
  33. ncbi Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations
    Stephanie Ma
    Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China
    Mol Cancer Res 6:1146-53. 2008
    ..ALDH, expressed along CD133, can more specifically characterize the tumorigenic liver CSC population...
  34. ncbi Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer
    Yasuyo Ohi
    Hakuaikai Sagara Hospital Department of Molecular and Cellular Pathology, Field of Oncology, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
    Histopathology 59:776-80. 2011
    ..However, the clinical significance of ALDH1 expression in triple-negative (TN) breast cancer, a high-risk breast cancer lacking the benefit of specific therapy, remains to be solved...
  35. ncbi The activity of class I, II, III, and IV alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in esophageal cancer
    Wojciech Jelski
    Department of Biochemical Diagnostics, Medical University, Waszyngtona 15 A, 15 269, Bialystok, Poland
    Dig Dis Sci 54:725-30. 2009
    ..In this study the activity of ADH isoenzymes and ALDH in esophageal cancer were compared with the activity in normal tissue.
  36. ncbi Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi
    Ying Jie Wang
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 114:299-310. 2003
    ..We propose that PI4KIIalpha establishes the Golgi's unique lipid-defined organelle identity by generating PI(4)P-rich domains that specify the docking of the AP-1 coat machinery...
  37. ncbi Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment
    Erika Resetkova
    Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 46202, USA
    Breast Cancer Res Treat 123:97-108. 2010
    ..The novel finding is that tumor microenvironment may play a significant role in determining the prognostic impact of stem/progenitor cells in human breast tumors...
  38. ncbi Multiple Rubisco forms in proteobacteria: their functional significance in relation to CO2 acquisition by the CBB cycle
    Murray Ronald Badger
    Molecular Plant Physiology Group, Research School of Biological Sciences, The Australian National University, Canberra, ACT, Australia
    J Exp Bot 59:1525-41. 2008
    ....
  39. pmc Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer
    H Nalwoga
    Section for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital, N 5021, Bergen, Norway
    Br J Cancer 102:369-75. 2010
    ..The aim of this study was to explore the expression of these proteins in breast cancers from an African population and their associations with the basal-like phenotype (BLP) and other molecular characteristics...
  40. ncbi Protein kinase C and the regulation of the actin cytoskeleton
    Christer Larsson
    Lund University, Dept of Laboratory Medicine, Molecular Medicine, Entrance 78, 3rd Floor, UMAS SE 205 02, Malmo University Hospital, Malmo, Sweden
    Cell Signal 18:276-84. 2006
    ..Their potential role in PKC effects on the cytoskeleton is discussed...
  41. pmc Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis
    M I Koukourakis
    Department of Radiotherapy Oncology, Democritus University of Thrace, Alexandroupolis 68100, Greece
    Br J Cancer 89:877-85. 2003
    ....
  42. ncbi Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2
    R A Gupta
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA
    Nat Rev Cancer 1:11-21. 2001
    ..Recent studies in humans indicate that therapy with specific COX-2 inhibitors might be an effective approach to colorectal cancer prevention and treatment...
  43. ncbi Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation
    Iris Helfrich
    Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
    J Invest Dermatol 127:782-91. 2007
    ..Indeed, inhibition of aPKC function showed that endogenous aPKC is crucial for in vitro barrier function and this required the presence of both the Par3 and Par6 binding sites...
  44. ncbi Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis
    Montserrat Camps
    Serono Pharmaceutical Research Institute, Serono International S A, 14, Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland
    Nat Med 11:936-43. 2005
    ..Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis...
  45. ncbi Protein kinase Ctheta: a new essential superstar on the T-cell stage
    A Altman
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    Immunol Today 21:567-73. 2000
    ..Among these, the nuclear factor-kappaB (NF-kappaB) signaling cascade appears to be the most critical target of PKCtheta in the T-cell receptor/CD28 costimulatory pathway that leads to T-cell activation...
  46. ncbi PKC inhibitors: potential in T cell-dependent immune diseases
    Gottfried Baier
    Department for Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
    Curr Opin Cell Biol 21:262-7. 2009
    ..Here we review the topic of PKC pathway activity in the regulation of T lymphocytes both in the cytokine response and adhesive capacity, and review recent results with PKC inhibitors in vitro and in vivo...
  47. ncbi Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Cdelta
    Robert V Stahelin
    Department of Chemistry, University of Illinois, Chicago, Illinois 60607, USA
    J Biol Chem 279:29501-12. 2004
    ..Collectively, these results provide new insight into the differential roles of C1 domains in the DAG-induced membrane activation of PKCdelta and the origin of its specific subcellular localization in response to DAG...
  48. ncbi Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo
    Kathleen M Leahy
    Pharmacia, Mail Zone AA4C, 700 Chesterfield Parkway, Chesterfield, Missouri 63017, USA
    Cancer Res 62:625-31. 2002
    ..2-3.0-fold) in response to celecoxib. Thus, the antitumor activity of celecoxib may be attributable, at least in part, to a direct effect on host stromal elements, such as the angiogenic vasculature...
  49. ncbi Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer
    Michael I Koukourakis
    Department of Radiotherapy Oncology, Democritus University of Thrace Medical School, 68100 Alexandroupolis, Greece
    Clin Exp Metastasis 22:25-30. 2005
    Lactate dehydrogenase 5 (LDH5) is one of the five LDH isoenzymes and, apparently, the most important for promoting anaerobic glycolysis. LDH5 is transcriptionally regulated by the hypoxia inducible factors (HIF) 1alpha and 2alpha...
  50. pmc Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol
    Ming Zhou
    Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA
    Mol Cancer 9:33. 2010
    ..In this study we investigated the role of LDH-A in mediating Taxol resistance in human breast cancer cells...
  51. ncbi Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis
    Yanislav Kolev
    Surgical Oncology Department, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Ann Surg Oncol 15:2336-44. 2008
    ..However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma...
  52. ncbi The role of protein kinase C activation and the vascular complications of diabetes
    Net Das Evcimen
    Ankara University, Pharmacy Faculty, Biochemistry Department, 06100 Ankara, Turkey
    Pharmacol Res 55:498-510. 2007
    ..PKC isoform selective inhibitors are likely new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease with very little side effects...
  53. ncbi Signalling by PI3K isoforms: insights from gene-targeted mice
    Bart Vanhaesebroeck
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Trends Biochem Sci 30:194-204. 2005
    ..Targeting strategies that take into account the complex interplay between members of the PI3K family will be crucial to gain a full understanding of the physiological roles of the isoforms of PI3K...
  54. ncbi Protein kinase C(theta) in T cell activation
    Noah Isakov
    Department of Microbiology and Immunology, Faculty of Health Sciences, and the Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
    Annu Rev Immunol 20:761-94. 2002
    ..The selective expression of PKC theta in T cells and its essential role in mature T cell activation establish it as an attractive drug target for immunosuppression in transplantation and autoimmune diseases...
  55. ncbi Expression of bone resorption genes in osteoarthritis and in osteoporosis
    Darja Bitenc Logar
    Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI 1000, Ljubljana, Slovenia
    J Bone Miner Metab 25:219-25. 2007
    ....
  56. pmc JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease
    Stephane Hunot
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 101:665-70. 2004
    ..Our data revealed that JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for neurodegeneration in PD...
  57. pmc Increased anxiety and altered responses to anxiolytics in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase
    S F Kash
    Departments of Medicine and Microbiology Immunology, and Hormone Research Institute, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 96:1698-703. 1999
    ..We propose that stress-induced GABA release is impaired in GAD65-deficient mice, resulting in increased anxiety-like responses and a diminished response to the acute effects of drugs that facilitate the actions of released GABA...
  58. ncbi Physiological roles of PKB/Akt isoforms in development and disease
    B Dummler
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
    Biochem Soc Trans 35:231-5. 2007
    ....
  59. ncbi Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance
    Kiyoko Fukami
    Laboratory of the Genome and Biosignals, Tokyo University of Pharmacy and Life Science, 1432 1 Horinouchi, Hachioji, Tokyo, Japan
    Prog Lipid Res 49:429-37. 2010
    ..In this review, we focus on the roles of PLC as a calcium-regulating enzyme and as a modulator of the phosphoinositide balance...
  60. ncbi Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer
    J M Mates
    Department of Biología Molecular y Bioquímica, Facultad de Ciencias, Campus de Teatinos, Universidad de Malaga, Malaga, Spain
    Curr Mol Med 13:514-34. 2013
    ..Thus, modulation of GA function may be a new therapeutic target for cancer treatment...
  61. ncbi The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes
    R Boer
    Byk Gulden Pharmaceuticals, Konstanz, Germany
    Mol Pharmacol 58:1026-34. 2000
    ..various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments...
  62. ncbi Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer
    Panayiotis A Theodoropoulos
    Department of Biochemistry, School of Medicine, University of Crete, Heraklion, Greece
    Cancer Lett 288:99-106. 2010
    ..7% of the CTCs analyzed in seven patients, were ALDH1(high)/CD24(-/low). In conclusion, we report the existence of a subpopulation of CTCs with putative stem cell progenitor phenotypes in patients with metastatic breast cancer...
  63. ncbi PKC-alpha regulates cardiac contractility and propensity toward heart failure
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Nat Med 10:248-54. 2004
    ..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure...
  64. pmc Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients
    Bahriye Aktas
    Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg Essen, Hufelandstrasse 55, 45122 Essen, Germany
    Breast Cancer Res 11:R46. 2009
    ....
  65. ncbi TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue
    D A Kujubu
    Department of Biological Chemistry, UCLA School of Medicine 90024
    J Biol Chem 266:12866-72. 1991
    ..The expression of the TIS10 gene appears to be highly cell type-restricted in cultured cell lines; of 12 cell lines tested under superinducing conditions, only the rodent embryonic Swiss 3T3 and Rat1 cell lines expressed TIS10 gene...
  66. ncbi Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling
    Marco Conti
    Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 943095 5317, USA
    Annu Rev Biochem 76:481-511. 2007
    ....
  67. pmc PKC-θ is a drug target for prevention of T cell-mediated autoimmunity and allograft rejection
    Myung Ja Kwon
    Beckman Research Institute of the City of Hope, Duarte, CA 91010, Los Angeles, USA
    Endocr Metab Immune Disord Drug Targets 10:367-72. 2010
    ..Since these effector T helper cells are responsible for mediating autoimmunity, selective inhibition of PKC-θ is considered a treatment for prevention of autoimmune diseases and allograft rejection...
  68. ncbi LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis
    Zhi Yu Wang
    School of Chinese Medicine, The University of Hong Kong, Estates Building, 10 Sassoon Road, Hong Kong, China
    Breast Cancer Res Treat 131:791-800. 2012
    ..Our results suggested that LDH-A inhibition might offer a promising therapeutic strategy for breast cancer...
  69. pmc Nonredundant functions for Akt isoforms in astrocyte growth and gliomagenesis in an orthotopic transplantation model
    Raelene Endersby
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 71:4106-16. 2011
    ..Taken together, these results indicate context-dependent roles for individual Akt isoforms and suggest that there may be heterogeneous tumor response to isoform-specific inhibitors...
  70. ncbi Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6
    H Enslen
    Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA
    J Biol Chem 273:1741-8. 1998
    ..The MKK3 and MKK6 signal transduction pathways are therefore coupled to distinct, but overlapping, groups of p38 MAP kinases...
  71. ncbi Regulation of protein kinase C
    A C Newton
    Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0640, USA
    Curr Opin Cell Biol 9:161-7. 1997
    ....
  72. ncbi Arylamine N-acetyltransferases: from structure to function
    Edith Sim
    Department of Pharmacology, University of Oxford, Oxford, United Kingdom
    Drug Metab Rev 40:479-510. 2008
    ..of human and rodent NAT enzymes and their genes is aiding our understanding of the roles of the individual isoenzymes. This may have clinical importance since human NAT1 is overexpressed in a sub-population of breast cancers and ..
  73. ncbi 5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression
    Alejandro Godoy
    Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
    Prostate 71:1033-46. 2011
    ..A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-reductase-3 protein expression and its cellular localization in human tissues remain unknown...
  74. ncbi Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Ciota
    Eda Erdogan
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Biol Chem 281:28450-9. 2006
    ..We conclude that ATM inhibits cellular transformation by selectively targeting Cys-69 within the PB1 domain of PKCiota...
  75. ncbi MK2 and MK3--a pair of isoenzymes?
    Natalia Ronkina
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, D30625 Hannover, Germany
    Front Biosci 13:5511-21. 2008
    ..MK2-knockout mice show decreased LPS-induced cytokine biosynthesis and increased protection against collagen-induced arthritis. Recently generated MK2/3 double knockout mice show further reduction of LPS-induced cytokine production...
  76. ncbi Inactivation of aPKClambda results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex
    Fumiyasu Imai
    Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3 9 Fuku ura, Kanazawa Ku, Yokohama 236 0004, Japan
    Development 133:1735-44. 2006
    ..Therefore, we concluded that, at least in the later stages of neurogenesis, regulation of cell cycle exit is independent of adherens junctions...
  77. pmc CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1
    Donghai Wang
    Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, New York 14214, USA
    Mol Cell Biol 24:164-71. 2004
    ..Together, these results indicate that CARMA1 mediates CD3/CD28 costimulation-induced NF-kappaB activation by recruiting downstream signaling components into the immunological synapse...
  78. ncbi Differential regulation of lipopolysaccharide-induced monocyte matrix metalloproteinase (MMP)-1 and MMP-9 by p38 and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases
    Wan Ching Lai
    Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 170:6244-9. 2003
    ..Moreover, p38 regulates MMP-1 mainly through a PGE(2)-dependent pathway, whereas ERK1/2-mediated MMP-1 and MMP-9 production involves the activation of additional MMP promoter sites through a PGE(2)-independent mechanism...
  79. ncbi Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells
    L A Selbie
    Garvan Institute of Medical Research, St Vincent s Hospital, Sydney, Australia
    J Biol Chem 268:24296-302. 1993
    ..As such, PKC iota is unlikely to be activated by the diacylglycerol that is derived from phosphoinositide hydrolysis, but might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion...
  80. pmc Protein kinase C betaII and PKCiota/lambda: collaborating partners in colon cancer promotion and progression
    Nicole R Murray
    Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    Cancer Res 69:656-62. 2009
    ..Thus, PKCbetaII and PKCiota, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively...
  81. pmc Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses
    Benjamin J Marsland
    Molecular Biomedicine, Swiss Federal Institute of Technology, Wagistr 27, CH8952 Zurich Schlieren, Switzerland
    J Exp Med 200:181-9. 2004
    ..Taken together, our results reveal a central role for PKC-theta signaling during Th2 responses...
  82. ncbi A novel small-molecule inhibitor of protein kinase Ciota blocks transformed growth of non-small-cell lung cancer cells
    Melody Stallings-Mann
    Department of Cancer Biology, Comprehensive Cancer Center, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Cancer Res 66:1767-74. 2006
    ..ATG and ATM will be useful reagents for studying PKCiota function in transformation and represent promising new agents for the clinical treatment of NSCLC...
  83. ncbi Hypoxia induces cyclooxygenase-2 via the NF-kappaB p65 transcription factor in human vascular endothelial cells
    J F Schmedtje
    Sealy Center for Molecular Cardiology, Department of Medicine, The University of Texas Medical Branch, Galveston 77555 1064, USA
    J Biol Chem 272:601-8. 1997
    ..Thus, the intracellular signaling mechanism that leads to induction of COX-2 by hypoxia includes binding of p65 to the relatively 3' NF-kappaB consensus element in the COX-2 upstream promoter region in human vascular endothelial cells...
  84. ncbi Keynote review: phosphodiesterase-4 as a therapeutic target
    Miles D Houslay
    Division of Biochemistry and Molecular Biology, IBLS, Wolfson Link Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, Scotland, UK
    Drug Discov Today 10:1503-19. 2005
    ..Here, we delineate the range of PDE4 isoforms, their role in signaling, their structural biology and related preclinical and clinical pharmacology...
  85. ncbi Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation
    Daniel J Weisenberger
    Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089 9181, USA
    Mol Cancer Res 2:62-72. 2004
    ..Methylation analyses of immunodeficiency, chromosomal instabilities, and facial abnormalities cells revealed that an Alu repeat sequence was highly methylated, suggesting that Alu sequences are not DNMT3b targets...
  86. ncbi Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson's disease
    P Teismann
    Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany
    Synapse 39:167-74. 2001
    To study the possible role of the isoenzymes of cyclooxygenase COX-1 and COX-2 in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease we used acetylsalicylic acid, a COX-1/COX-2 inhibitor, in ..
  87. pmc Treatment of Fabry disease: outcome of a comparative trial with agalsidase alfa or beta at a dose of 0.2 mg/kg
    Anouk C Vedder
    Department of Internal Medicine Endocrinology and Metabolism, Academic Medical Center, Amsterdam, Netherlands Department of Medical Biochenmistry, Academic Medical Center University of Amsterdam, Amsterdam, Netherlands
    PLoS ONE 2:e598. 2007
    ..We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial...
  88. ncbi Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa
    Michelle Krisfalusi
    Laboratory for Reproductive Biology, University of North Carolina School of Medicine, NC 27599, USA
    Biol Reprod 75:270-8. 2006
    ..These data support a role for the fibrous sheath as a scaffold for anchoring multiple glycolytic enzymes along the length of the flagellum to provide a localized source of ATP that is essential for sperm motility...
  89. ncbi Characterization of the genomic structure, chromosomal location and promoter of human prostaglandin H synthase-2 gene
    R Tazawa
    Division of Hematology, University of Texas Houston 77030
    Biochem Biophys Res Commun 203:190-9. 1994
    ..Studies of the promoter activity showed that the first 460 nucleotides of 5'-flanking region efficiently drove transcription of the luciferase reporter gene in human umbilical vein endothelial cells upon stimulation with phorbor ester...
  90. pmc The 4-coumarate:CoA ligase gene family in Arabidopsis thaliana comprises one rare, sinapate-activating and three commonly occurring isoenzymes
    Björn Hamberger
    Max Planck Institute for Plant Breeding Research, Carl von Linne Weg 10, 50829 Cologne, Germany
    Proc Natl Acad Sci U S A 101:2209-14. 2004
    ..Various characteristics shared by all known plant 4CL genes, as well as by the encoded proteins, define and delimit the At4CL gene family and distinguish it from the closely related family of "At4CL-like" genes...
  91. pmc Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer
    Astrid M Eder
    Department of Molecular Therapeutics, M D Anderson Cancer Center, University of Texas, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 102:12519-24. 2005
    ..These results implicate PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCiota is a novel target for therapy...
  92. ncbi Protein kinase C isozymes and the regulation of diverse cell responses
    E C Dempsey
    Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Am J Physiol Lung Cell Mol Physiol 279:L429-38. 2000
    ..More specific approaches for studying PKC isozymes and their role in cell responses have been developed. Strengths and weaknesses of different experimental strategies are reviewed. Future directions for investigation are identified...
  93. pmc Protein kinase Ciota is required for Ras transformation and colon carcinogenesis in vivo
    Nicole R Murray
    Mayo Clinic Comprehensive Cancer Center, Griffin Cancer Research Building, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
    J Cell Biol 164:797-802. 2004
    ..Our data demonstrate that PKCiota is required for oncogenic Ras- and carcinogen-mediated colon carcinogenesis in vivo and define a procarcinogenic signaling axis consisting of Ras, PKCiota, and Rac1...
  94. ncbi Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes
    N Goode
    Imperial Cancer Research Fund, Lincoln s Inn Fields, London, United Kingdom
    J Biol Chem 267:16878-82. 1992
    ..Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta...
  95. ncbi Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets
    Vincent Jaquet
    Department of Pathology and Immunology, Centre Medical Universitaire, School of Pharmaceutical Sciences, University of Geneva, Switzerland
    Antioxid Redox Signal 11:2535-52. 2009
    ..We conclude that NOX inhibition is a pertinent and promising novel pharmacologic concept, but that major efforts will be necessary to develop specific NOX inhibitors suited for clinical application...
  96. pmc Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair
    Xinping Zhang
    The Center for Musculoskeletal Research, University of Rochester Medical Center, New York 14642, USA
    J Clin Invest 109:1405-15. 2002
    ..These results provide a model whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal skeletal repair...
  97. ncbi Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family
    Zhao Xia Chen
    Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
    J Cell Biochem 95:902-17. 2005
    ..This article contains Supplementary Material available at http://www.mrw.interscience.wiley.com/suppmat/0730-2312/suppmat/2005/95/chen.html...
  98. ncbi Crucial importance of PKC-beta(I) in LFA-1-mediated locomotion of activated T cells
    Y Volkov
    Dublin Molecular Medicine Centre, Trinity College, Dublin 8, Ireland
    Nat Immunol 2:508-14. 2001
    ..These observations may have physiological equivalents at advanced (post-integrin activation) stages of lymphocyte extravasation...
  99. ncbi Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease
    Dominique P Germain
    Assistance Publique Hopitaux de Paris, Paris, France
    J Am Soc Nephrol 18:1547-57. 2007
    ..Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types...
  100. ncbi Specificity in the cAMP/PKA signaling pathway. Differential expression,regulation, and subcellular localization of subunits of PKA
    B S Skalhegg
    Institute for Nutrition Reserarch, University of Oslo, Norway
    Front Biosci 5:D678-93. 2000
    ..Here we will describe features of this signaling pathway that may contribute to explain how differential effects of cAMP may be contributed to features of the PKA signaling pathway...
  101. ncbi Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression
    Koji Morimoto
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan
    Cancer Sci 100:1062-8. 2009
    ..Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are characterized by ER-, Ki67-, and HER2+...

Research Grants64

  1. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    ..SAMe biosynthesis due to decreased MAT1A mRNA levels and post-translational inhibition of the MAT1A-encoded isoenzymes. Chronic hepatic SAMe deficiency occurs in MAT1A knockout (KO) mice, which exhibit increased propensity to ..
  2. Prostate cancer prevention by selenium supplementation
    Rayudu Gopalakrishna; Fiscal Year: 2012
    ..Advanced tumor cells escape the cancer-preventive actions of selenium via the increased expression of PKC isoenzymes (Se- sensitive 1or Se-resistant 5) and selenoprotein (TR) which naturally occurs in tumor progression...
  3. Novel Functions of S1P in Neuroinflammation
    TOMASZ K KORDULA; Fiscal Year: 2013
    ..We have shown that IL-1 stimulates and upregulates sphingosine kinase 1 (SphK1), one of the two isoenzymes that generate sphingosine-1-phosphate (S1P), a lipid mediator that regulates diverse cellular processes ..
  4. ROLE AND REGULATION OF PROTEIN KINASE C ISOENZYMES
    Yusuf Awni Hannun; Fiscal Year: 2013
    ..notably through phospholipase D (PLD), it does not distinguish mechanisms for regulating activation of specific isoenzymes, and it focuses only on the plasma membrane as a site for PKC action...
  5. Regulation of Nox Enzymes by Calcium and Novel Subunits
    J Lambeth; Fiscal Year: 2009
    ..The seven human Nox isoenzymes reflect three modes of regulation: 1) constitutively active (Nox4);2) activation by assembly with regulatory ..
  6. Regulation of Nox Enzymes by Calcium and Novel Subunits
    JOHN DAVID LAMBETH; Fiscal Year: 2013
    ..The seven human Nox isoenzymes reflect three modes of regulation: 1) constitutively active (Nox4);2) activation by assembly with regulatory ..
  7. Sex-specific fetal programming of adult vascular dysfunction and hypertension
    KUNJU REDDIAR SATHISH KUMAR; Fiscal Year: 2013
    ..utero T exposure will cause gender-specific hypertensive effects through upregulation of distinct vascular PKC isoenzymes and differential endothelial dysfunctions in the male and female vasculature, which may be regulated through ..
  8. REGULATION AND FUNCTIONS OF METHIONINE ADENOSYLTRANSFERASE GENES IN LIVER
    SHELLY CHI LOO LU; Fiscal Year: 2013
    ..chronic liver disease have reduced hepatic SAMe level due to decreased expression and activity of MAT1A- encoded isoenzymes. To better understand the in vivo significance, we created the MAT1A knockout (KO) mouse model...
  9. Mechanisms of abdominal aortic aneurysm formation
    Alan Daugherty; Fiscal Year: 2010
    ..Project 4 (Nancy R. Webb) will determine the role of specific isoenzymes of secretory phospholipase A2s in promoting inflammation at the site of macrophage recruitment during the ..
  10. Intracellular Target of Sphingosine-1-Phosphate
    GRAHAM M STRUB; Fiscal Year: 2010
    ..Cellular localizations of the two SphK isoenzymes that produce S1P, SphK1 and SphK2, have begun to provide some clues...
  11. Pharmacological characterization of a novel ROCK inhibitor for COPD
    Xiaoming Zhang; Fiscal Year: 2010
    ..Theron has identified a highly potent inhibitor of the human ROCK-1 and ROCK-2 isoenzymes. The purpose of this proposal is to further characterize the lead inhibitor TRN-101 in models that are relevant ..
  12. Aortic Aneurysm Formation: Mechanisms of Oxidative Stress-Induced MMP Expression
    MATTHEW JEREMIAH EAGLETON; Fiscal Year: 2012
    ..expression in aortic smooth muscle cells and macrophages;2) Define the mechanisms by which activated PKC-isoenzymes regulate MMP expression, specifically addressing the roles of STAT1 and STATS, members of the JAK/STAT pathway;..
  13. UDP-Glucuronosyltransferases in responses to environmental and endogenous toxins
    Beverly H Koller; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The UDP glucuronosyltransferase isoenzymes (UGT) are critical for the detoxification and elimination of structurally diverse lipophilic molecules including products of normal cellular metabolism, ..
  14. Safety, Efficacy, and Mechanisms in American Ginseng in HIV-Related Fatigue
    Adriana S A Andrade; Fiscal Year: 2012
    ..Herb-ARV interactions primarily involve the modulation of ARV-metabolizing cytochrome P450 (CYP450) isoenzymes, which in turn can alter drug efficacy and/or toxicity...
  15. PKC Isoenzymes and Diabetic Microvascular Hyperpermeability
    Sarah Y Yuan; Fiscal Year: 2010
    ..abstract_text> ..
  16. Role of 5-alpha Reductase in Testosterone Actions
    Shalendar Bhasin; Fiscal Year: 2007
    ..potent 5-alpha reductase inhibitor (duasteride) that inhibits both type 1 and type 2 steroid 5-alpha -reductase isoenzymes. Healthy young men, 21-40 years of age, will be treated with a long acting GnRH agonist to suppress endogenous ..
  17. INTESTINAL AND COLONIC CYTOCHROME P450 GENE EXPRESSION
    Peter Traber; Fiscal Year: 1993
    ..Cytochrome P450 isoenzymes, which are encoded by a large superfamily of related genes play an important role in the metabolism of ..
  18. REGULATION OF PHOSPHOLIPASE C
    T Harden; Fiscal Year: 2002
    ..The possibility that one or more of the PLC isoenzymes is activated by pertussis toxin- sensitive G-proteins will be examined by reconstitution with recombinant G(..
  19. CARDIAC MUSCLE CELL DEVELOPMENT AND NUCLEAR PROTEINS
    JASWANT BHORJEE; Fiscal Year: 1990
    ..The neonatal cardiomyocytes in culture exhibit the developmentally regulated profiles of the myosin isoenzymes in the presence of thyroid hormones...
  20. TWO TYPES OF MONOAMINE OXIDASE
    Jean Shih; Fiscal Year: 2007
    ..the[unreadable] regulation and the in-vivo function of monoamine oxidase (MAO) A and B,[unreadable] which are isoenzymes important for the degradation of monoamine[unreadable] neurotransmitters and biogenic amines...
  21. STUDIES ON ADENOSINE TRIPHOSPHATE TRANSPHOSPHORYLASES
    THOMAS ALBER; Fiscal Year: 1990
    ..These studies include the following series of enzymes: adenylate kinase isoenzymes from rabbit and calf; nucleoside diphosphokinase from yeast; creatine kinase isoenzymes from rabbit and calf; ..
  22. Flavocoxid: A Medical Food Therapy for Osteoarthritis
    Sarah Morgan; Fiscal Year: 2004
    ..Conventional non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-1 and COX-2 isoenzymes, but have a marginal or no effect on 5-LO...
  23. Implementing Newborn Screening for Duchenne Muscular Dystrophy in the Community
    Jerry Mendell; Fiscal Year: 2009
    ..the range of creatine kinase (CK) observed on >30,000 anonymous samples, a successful method to measure CK isoenzymes, with particular emphasis on CK-MB, and a reliable method of DNA analysis of the dystrophin gene, with ..
  24. Canthinones as Human Isozyme Selective PDE4 Inhibitors
    KEVIN CZERWINSKI; Fiscal Year: 2002
    ..of substituted canthin-6-one and canthin-5, 6-dione indole alkaloids against human cAMP phosphodiesterase (PDE4) isoenzymes. In the past canthin-6-one indole alkaloids have been shown to elicit inhibitory activity against bovine PDE4 ..
  25. PDE3 Inhibitors: Selective Blockers of Oocyte Maturation
    Jeffrey Jensen; Fiscal Year: 2007
    ..The goal of this aim is to characterize the PDE isoenzymes expressed in the macaque ovary...
  26. Regulation of the Contraction in Human Uterus
    VICTOR FOMIN; Fiscal Year: 2004
    ..PKC action on myometrium can be explained by diversity within the PKC family of proteins, consisting of 12 known isoenzymes (isoforms)...
  27. CAUSES AND EFFECTS OF ARGINASE ACTIVITY AFTER TRAUMA
    Juan Ochoa; Fiscal Year: 2001
    ..evaluate the temporal response of arginase activity after trauma, define the patterns of response of the two isoenzymes, and establish the cells and tissues where it is expressed, 2) Identify "factors" that increase arginase ..
  28. PROTEIN KINASE C AND GLIAL TUMOR GROWTH
    Ian Pollack; Fiscal Year: 1999
    ..The experimental strategy is designed to identify which PKC isoenzymes are overexpressed in neoplastic astrocytes in comparison to non-neoplastic astrocytes using immunohistochemical ..
  29. ACTIVE SITES OF CREATINE KINASE FROM HEART AND MUSCLE
    GEORGE KENYON; Fiscal Year: 1999
    ..Within the human cell, two cytosolic and two mitochondrial isoenzymes interact with different cellular structures, and evidence suggests that this intracellular localization has ..
  30. ISOFORMS OF CREATINE KINASE--MYOCARDIAL INFARCATION
    Dana Abendschein; Fiscal Year: 1991
    ..However, conventional methods including detection of changes in activity of total creatine kinase (CK) or its isoenzymes in plasma are neither rapid nor sufficiently sensitive to permit reliable, early diagnosis...
  31. PROPERTIES OF DYNEIN ISOENZYMES
    Ian Gibbons; Fiscal Year: 2003
    ....
  32. DEVELOPMENTAL ALTERATIONS IN CARDIAC PROTEIN TURNOVER
    Allen Samarel; Fiscal Year: 2003
    ..indicates that neurohomonal and mechanical stimuli that induce sarcomeric assembly activate the novel PKC isoenzymes PKC-delta and PKC-epsilon. PKC activation may also be necessary for FAK activation and focal adhesion formation...
  33. STRUCTURAL BASIS OF SPERMATOZOAN MOTILITY
    Ian Gibbons; Fiscal Year: 1991
    ..different roles of the individual two-headed domains on each cross bridge, as well as the less well studied isoenzymes of the inner dynein arm...
  34. KINETICS OF RETINOID METABOLISM BY ALCOHOL DEHYDROGENASE
    Carol Stone; Fiscal Year: 2000
    ..It has been hypothesized that human cytosolic alcohol dehydrogenase isoenzymes in the stomach and liver function as physiological enzymes in retinoid metabolism, and that ingested ethanol ..
  35. STRUCTURE AND FUNCTION IN PATHOGENIC YEAST ENVELOPES
    WILFRED ARNOLD; Fiscal Year: 1990
    ..The "isoenzymes" are also distinguished by different responses to inhibitors (NaF, phosphate and tartrate)...
  36. TWO ISOFORMS OF NA,K-ATPASE IN THE HEART
    Yuk Chow Ng; Fiscal Year: 1992
    ..Inhibition of the isoenzymes by ouabain caused biphasic positive inotropic effects indicating that both of the alpha subunits are the ..
  37. ANTINEOPLASTIC DRUG HEPATIC INTERACTIONS
    Dean Brenner; Fiscal Year: 1990
    ..and drug induced toxicity due to variation in local cellular con-centrations of drug specific metabolizing isoenzymes. 2) Compounds which inhibit or induce hepatic drug metabolizing enzymes will pertrub the metabolism of ..
  38. DEOXYCYTIDINE KINASE: REGULATION & MOLECULAR BIOLOGY
    DAVID IVES; Fiscal Year: 1991
    ..However, it has not been clear which protein, of several isoenzymes reported, is responsible for phosphorylating each drug, nor is it known whether such isoenzymes are distinct ..
  39. MECHANISTIC STUDIES OF PHOSPHOLIPID PHOSPHODIESTERASES
    Stephen Martin; Fiscal Year: 1999
    ..goal of this research program is to elucidate the function and mechanism of action of bacterial and mammalian isoenzymes that hydrolyze the phosphodiester bonds of different classes of phospholipids and to discover novel inhibitors ..
  40. INTERFERON ANIMAL VIRUSES AND PROTEIN SYNTHESIS
    Peter Lengyel; Fiscal Year: 1999
    ..The induced proteins include enzymes, e.g., at least four (2'-5') oligoadenylate synthetase isoenzymes and eIF-2 kinase. The listed enzymes are latent unless activated by binding double-stranded RNA...
  41. Novel ALT Isoenzymes and Their Diagnositc Application
    Da Wei Gong; Fiscal Year: 2003
    ..Importantly, the two isoenzymes are encoded by distinct genes and differ significantly in tissue distribution; ALT2 is highly expressed in ..
  42. HUMAN HEPATIC & INTESTINAL UDP GLUCURONOSYLTRANSFERASES
    Anna Radominska Pandya; Fiscal Year: 2002
    ..UGTs of the 2B family and to compare them with hepatic UGT2B enzymes, with primary emphasis on steroid-directed isoenzymes. The central hypothesis to be tested is that the human intestine is involved in the biotransformation of ..
  43. STRUCTURE-BASED LIGAND DESIGN FOR ALCOHOL DEHYDROGENASE
    Thomas Hurley; Fiscal Year: 2000
    ..to identify specific inhibitors and substrates for the human beta, gamma, and sigma alcohol dehydrogenase (ADH) isoenzymes. Dietary and biogenic alcohols and aldehydes are primarily metabolized by the NAD(H) dependent alcohol ..
  44. STRUCTURE/FUNCTION OF LIVER ALCOHOL DEHYDROGENASES
    WILLIAM BOSRON; Fiscal Year: 2001
    ..encoded subunits of alcohol dehydrogenase which combine to form more than 20 different active dimeric isoenzymes. We have shown that the kinetic properties of these isoenzymes differ widely...
  45. SURGICAL HEPATECTOMY--PROLACTIN INITIATES MITOGENESIS
    CHARLES PUTNAM; Fiscal Year: 1993
    ..More recently, a 'second messenger' of prolactin action, protein kinase C (PKC), has been identified. PKC isoenzymes are modulated by membrane phospholipid products (i.e...
  46. STRUCTURE & FUNCTION OF LIVER ALCOHOL DEHYDROGENASES
    WILLIAM BOSRON; Fiscal Year: 1992
    ..encoded subunits of alcohol dehydrogenase which combine to form more than 20 different active dimeric isoenzymes. We have shown that the kinetic properties of these isoenzymes differ widely...
  47. GSTP1 gene repression in prostate cancer
    Rakesh Singal; Fiscal Year: 2004
    Glutathione S-transferases (GSTs) are a group of isoenzymes that catalyze intracellular detoxification reactions by conjugating glutathione with electrophilic compounds including carcinogens and exogenous drugs...
  48. Effect of ethanol on retinoid metabolism and signaling in zebrafish embryos
    WILLIAM BOSRON; Fiscal Year: 2007
    ..initially alcohol dehydrogenase and eventually aldehyde dehydrogenase and microsomal ethanol oxidizing CYP isoenzymes) in human tissues (liver and esophagus)...
  49. CONTRACTILE MECHANISMS IN ESOPHAGEAL SMOOTH MUSCLE
    Debra Helper; Fiscal Year: 1991
    ..A major hypothesis to be tested is that isoenzymes of actin, interacting with key actin-binding proteins (i.e...
  50. MOLECULAR PROBES FOR STUDIES OF MONOCLONALITY
    WALTER NAGEL; Fiscal Year: 1991
    ..from monoclonal expansion of smooth muscle cells; the determinant marker being electrophoretically separable isoenzymes of G-6-PD...
  51. NITRIC OXIDE, OSTEOCLASTS AND METABOLIC BONE DISEASE
    Philip Osdoby; Fiscal Year: 2004
    ..NO is formed from L-arginine in an oxidative reaction catalyzed by NO synthase (NOS) isoenzymes that are either constitutively expressed and calcium-activated (endothelial eNOS and neuronal nNOS isoforms), or ..
  52. High Resolution Ultrasound Biomicroscopy System
    Daniel Bernstein; Fiscal Year: 2005
    ..under current investigation include those with alterations of: a and b-adrenergic receptors, protein kinase C isoenzymes, the apelin/APJ-receptor, microtubule-associated protein light chain 3 (LC3), the calcium binding protein S100A4/..
  53. NA-K-ATPASE AND NEURONAL EXCITOTOXICITY IN EPLIEPSY
    Richard Robbins; Fiscal Year: 1992
    ..Three different mammalian genes encode this family of structurally similar heterodimeric isoenzymes which are responsible for ionic and osmotic equilibrium...
  54. STUDIES OF ENZYMES OF METABOLIC AND GENETIC INTEREST
    STEPHEN KUBY; Fiscal Year: 1980
    Physicochemical studies are being continued on the creatine phosphokinase isoenzymes isolated from the brain, heart and skeletal muscle of terminal patients with duchenne (x-linked) progressive muscular dystrophy...
  55. VASCULAR SMOOTH MUSCLE AND ENDOTHELIAL PROTEIN KINASE C
    J Ware; Fiscal Year: 2000
    ..PKC, rather than being a single enzyme, is a family of related but structurally distinct isoenzymes encoded by different genes and with different cofactor requirements and substrates...
  56. Role of Nitric Oxide in the Progression of Murine Cancer
    Rose Fife; Fiscal Year: 2002
    ..Three isoenzymes of nitric oxide synthase (NOS) are responsible for the synthesis of NO from arginine in the organism: ..
  57. GSH MEDIATED MECHANISMS IN NITROSOUREA TOXIC EFFECTS
    DONALD DE LUCA; Fiscal Year: 1990
    ..Studies are designed to establish whether GSH transferase isoenzymes from human liver and erythrocytes catalyze the synthesis of GS-I from BCNU or limit the formation of GS-I by ..
  58. Quantification of human alcohol metabolizing enzymes by mass spectrometry
    WILLIAM BOSRON; Fiscal Year: 2009
    ..coli and using their peptide MRM transitions to quantify specific isoenzymes as well as groups of isoenzymes...
  59. REGULATION OF GENES BY T AND DHT IN RAT AND HUMAN PROSTA
    Michael McPhaul; Fiscal Year: 2001
    ..Studies of patients deficient in one of the two isoenzymes that catalyze the conversion of T to DHT, as well as animal studies using specific inhibitors of 5a-reductase, ..
  60. NOVEL GST AND DETOXICATION OF DIOL EPOXIDES
    Shivendra Singh; Fiscal Year: 2006
    ..Recent studies from our laboratory and by others led us to hypothesize that the Alpha class GST isoenzymes play an important role in diol epoxide inactivation in human tissues...
  61. PROPERTIES OF DYNEIN ISOENZYMES
    Ian Gibbons; Fiscal Year: 2007
    ..abstract_text> ..
  62. BLOOD NO REFLOW AFTER MICROSURGICAL RECONSTRUCTION
    JAMES URBANIAK; Fiscal Year: 2004
    ..with nitric oxide donor and/or selective pharmacological manipulation of nitric oxide synthase (NOS) isoenzymes will reduce the incidence of reperfusion failure...
  63. PROPERTIES OF DYNEIN ISOENZYMES
    Ian Gibbons; Fiscal Year: 1980
    ..Steady-state and presteady-state kinetics of the two dynein isoenzymes are being studied in order to clarify the steps in the dynein cross-bridge cycle that generates active slidng ..
  64. THE TRANSCRIPTIONAL REGULATION OF MONOAMINE OXIDASE A
    Jean Shih; Fiscal Year: 2008
    ..Co-regulators interacting with APJGR during agonist stimulated or basal state will be co-immuno-precipitated by AR or GR specific antibody. The validity and the function of identified protein(s) will be investigated. ..