glucuronidase

Summary

Top Publications

  1. pmc FGF23 induces left ventricular hypertrophy
    Christian Faul
    Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
    J Clin Invest 121:4393-408. 2011
  2. ncbi Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23
    Kenneth Lim
    Brigham and Women s Hospital, Harvard Medical School, Room 120, 41 Ave Louis Pasteur, Boston, MA 02115, USA
    Circulation 125:2243-55. 2012
  3. pmc Suppression of aging in mice by the hormone Klotho
    Hiroshi Kurosu
    Department of Pathology, University of Texas UT Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390 9072, USA
    Science 309:1829-33. 2005
  4. ncbi Klotho converts canonical FGF receptor into a specific receptor for FGF23
    Itaru Urakawa
    Pharmaceutical Research Laboratories, Kirin Brewery Co, Ltd, 3 Miyahara, Takasaki, Gunma 370 1295, Japan
    Nature 444:770-4. 2006
  5. pmc Multilevel interactions between ethylene and auxin in Arabidopsis roots
    Anna N Stepanova
    Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA
    Plant Cell 19:2169-85. 2007
  6. pmc Klotho deficiency causes vascular calcification in chronic kidney disease
    Ming Chang Hu
    Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8885, USA
    J Am Soc Nephrol 22:124-36. 2011
  7. ncbi Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis
    Neta Ilan
    Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, P O Box 9649, Haifa 31096, Israel
    Int J Biochem Cell Biol 38:2018-39. 2006
  8. pmc Regulation of fibroblast growth factor-23 signaling by klotho
    Hiroshi Kurosu
    Department of Pathology, Pediatrics, and Internal Medicine and Applied Genomics, Genzyme Corporation, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 281:6120-3. 2006
  9. pmc Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy
    Hye Eun Yoon
    Division of Nephrology, Department of Internal Medicine, Incheon St Mary s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
    Nephrol Dial Transplant 26:800-13. 2011
  10. pmc Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice
    Shigehiro Doi
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:8655-65. 2011

Detail Information

Publications318 found, 100 shown here

  1. pmc FGF23 induces left ventricular hypertrophy
    Christian Faul
    Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
    J Clin Invest 121:4393-408. 2011
    ..These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD...
  2. ncbi Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23
    Kenneth Lim
    Brigham and Women s Hospital, Harvard Medical School, Room 120, 41 Ave Louis Pasteur, Boston, MA 02115, USA
    Circulation 125:2243-55. 2012
    ..FGF-23 levels rise in chronic kidney disease (CKD) despite progression of accelerated vascular calcification. There are currently conflicting data on whether FGF-23 may exhibit direct vasculoprotective effects in CKD...
  3. pmc Suppression of aging in mice by the hormone Klotho
    Hiroshi Kurosu
    Department of Pathology, University of Texas UT Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390 9072, USA
    Science 309:1829-33. 2005
    ..Klotho protein may function as an anti-aging hormone in mammals...
  4. ncbi Klotho converts canonical FGF receptor into a specific receptor for FGF23
    Itaru Urakawa
    Pharmaceutical Research Laboratories, Kirin Brewery Co, Ltd, 3 Miyahara, Takasaki, Gunma 370 1295, Japan
    Nature 444:770-4. 2006
    ..Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors...
  5. pmc Multilevel interactions between ethylene and auxin in Arabidopsis roots
    Anna N Stepanova
    Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA
    Plant Cell 19:2169-85. 2007
    ..This model not only implies existence of several levels of interaction but also provides a likely explanation for the strong ethylene response defects observed in auxin mutants...
  6. pmc Klotho deficiency causes vascular calcification in chronic kidney disease
    Ming Chang Hu
    Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8885, USA
    J Am Soc Nephrol 22:124-36. 2011
    ..Klotho ameliorates vascular calcification by enhancing phosphaturia, preserving glomerular filtration, and directly inhibiting phosphate uptake by vascular smooth muscle. Replacement of Klotho may have therapeutic potential for CKD...
  7. ncbi Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis
    Neta Ilan
    Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, P O Box 9649, Haifa 31096, Israel
    Int J Biochem Cell Biol 38:2018-39. 2006
    ..We also discuss clinical aspects and strategies for the development of heparanase inhibitors...
  8. pmc Regulation of fibroblast growth factor-23 signaling by klotho
    Hiroshi Kurosu
    Department of Pathology, Pediatrics, and Internal Medicine and Applied Genomics, Genzyme Corporation, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 281:6120-3. 2006
    ..Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23...
  9. pmc Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy
    Hye Eun Yoon
    Division of Nephrology, Department of Internal Medicine, Incheon St Mary s Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
    Nephrol Dial Transplant 26:800-13. 2011
    ..It is suggested that activation of renin-angiotensin system (RAS) or oxidative stress suppresses Klotho in the kidney. This study evaluated the association between Klotho expression and RAS in cyclosporine (CsA)-induced renal injury...
  10. pmc Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice
    Shigehiro Doi
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 286:8655-65. 2011
    ..These results have raised the possibility that secreted Klotho may function as an endogenous anti-EMT factor by inhibiting multiple growth factor signaling pathways simultaneously...
  11. ncbi Severely reduced production of klotho in human chronic renal failure kidney
    N Koh
    Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Konoe cho, Yoshida, Sakyo ku, Kyoto, 606 8501, Japan
    Biochem Biophys Res Commun 280:1015-20. 2001
    ..These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients...
  12. ncbi Development of series of gateway binary vectors, pGWBs, for realizing efficient construction of fusion genes for plant transformation
    Tsuyoshi Nakagawa
    Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu, Matsue, Japan
    J Biosci Bioeng 104:34-41. 2007
    ..The reporters employable in this system are beta-glucuronidase (GUS), synthetic green fluorescent protein with S65T mutation (sGFP), luciferase (LUC), enhanced yellow ..
  13. pmc Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet
    Wei Ling Lau
    Department of Nephrology, University of Washington, Seattle, Washington 98195, USA
    Kidney Int 82:1261-70. 2012
    ..Thus, klotho and osteopontin were upregulated by VDRA therapy in chronic kidney disease, independent of changes in serum parathyroid hormone and calcium...
  14. pmc Regulation and function of the FGF23/klotho endocrine pathways
    Aline Martin
    University of Tennessee Health Science Center, Memphis, Tennessee, USA
    Physiol Rev 92:131-55. 2012
    ..This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts...
  15. ncbi Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus
    Qian Zhang
    Genelux Corporation, San Diego Science Center, San Diego, California 92109, USA
    Cancer Res 67:10038-46. 2007
    ..cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) into the F14...
  16. pmc Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule
    Ming Chang Hu
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 8885, USA
    FASEB J 24:3438-50. 2010
    ..Transport inhibition can be mimicked by recombinant beta-glucuronidase and is associated with proteolytic degradation and reduced surface NaPi-2a...
  17. ncbi KL1 internal repeat mediates klotho tumor suppressor activities and inhibits bFGF and IGF-I signaling in pancreatic cancer
    Lilach Abramovitz
    Institute of Oncology, The Chaim Sheba Medical Center, Ramat Gan, Tel Aviv, Israel
    Clin Cancer Res 17:4254-66. 2011
    ..Klotho is expressed in the normal pancreas and both the IGF-I and FGF pathways are involved in pancreatic cancer development. We, therefore, undertook to study the expression and activity of klotho in pancreatic cancer...
  18. pmc Heparanase and syndecan-1 interplay orchestrates fibroblast growth factor-2-induced epithelial-mesenchymal transition in renal tubular cells
    Valentina Masola
    Department of Experimental Biomedical Sciences, University of Padova, 35122 Padova, Italy
    J Biol Chem 287:1478-88. 2012
    ..In conclusion, heparanase plays a role in the tubular-interstitial compartment favoring the FGF-2-dependent EMT of tubular cells. Hence, heparanase is an interesting pharmacological target for the prevention of renal fibrosis...
  19. ncbi The heparanase system and tumor metastasis: is heparanase the seed and soil?
    Gil Arvatz
    Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, P O Box 9649, Haifa, 31096, Israel
    Cancer Metastasis Rev 30:253-68. 2011
    ..In addition, cathepsin L is held responsible for processing and activation of heparanase, an endo-β-glucuronidase capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans, activity that is strongly ..
  20. ncbi Decreased expression of klotho gene in uremic atherosclerosis in apolipoprotein E-deficient mice
    Jie Yu
    Department of Cardiovasology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
    Biochem Biophys Res Commun 391:261-6. 2010
    ..These results suggested that CRF favored atherosclerosis in apo-E(-/-) mice and uremic atherosclerosis was accompanied by down-regulation of klotho expression...
  21. ncbi Tumor suppressor p53 regulates heparanase gene expression
    L Baraz
    Department of Oncology, Hadassah University Medical Center, Jerusalem, Israel
    Oncogene 25:3939-47. 2006
    ....
  22. pmc Role of Klotho in aging, phosphate metabolism, and CKD
    George B John
    Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9072, USA
    Am J Kidney Dis 58:127-34. 2011
    ..This review focuses on the current understanding of Klotho protein function, with emphasis on its potential involvement in the pathophysiologic process of CKD...
  23. pmc Heparanase is essential for the development of diabetic nephropathy in mice
    Natali Gil
    Sharett Institute, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Diabetes 61:208-16. 2012
    ..Our results collectively underscore the crucial role of heparanase in the pathogenesis of DN and its potential as a highly relevant target for therapeutic interventions in patients with DN...
  24. pmc Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis
    Madhuchhanda Roy
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Cell Biochem 106:200-9. 2009
    ..The enzyme acts as an endo-beta-D-glucuronidase resulting in HS fragments of discrete molecular weight size...
  25. pmc Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis
    Anurag Purushothaman
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Blood 115:2449-57. 2010
    ....
  26. pmc Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17
    Ci Di Chen
    Departments of Biochemistry, Pharmacology, and Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    Proc Natl Acad Sci U S A 104:19796-801. 2007
    ..Insulin enhances KL shedding without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it acts by stimulating their proteolytic activities...
  27. ncbi Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein
    Y Matsumura
    Division of Molecular Genetics, National Institute of Neuroscience, NCNP, Tokyo, Japan
    Biochem Biophys Res Commun 242:626-30. 1998
    ..Expression of the putative secreted form predominates over that of the membrane form. The present study provides fundamental information necessary for further analyses of the human kl gene and its functions...
  28. pmc The parathyroid is a target organ for FGF23 in rats
    Iddo Z Ben-Dov
    Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    J Clin Invest 117:4003-8. 2007
    ..These data indicate that FGF23 acts directly on the parathyroid through the MAPK pathway to decrease serum PTH. This bone-parathyroid endocrine axis adds a new dimension to the understanding of mineral homeostasis...
  29. ncbi Identification of sulfated oligosaccharide-based inhibitors of tumor growth and metastasis using novel in vitro assays for angiogenesis and heparanase activity
    C R Parish
    Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra
    Cancer Res 59:3433-41. 1999
    ..Acute hematogenous metastasis assays also demonstrated that PI-88 was a potent (>90%) inhibitor of blood-borne metastasis. Thus, by the use of novel in vitro screening procedures, we have identified a promising antitumor agent...
  30. ncbi Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system
    Hiroshi Tsujikawa
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Mol Endocrinol 17:2393-403. 2003
    ..These observations suggest that klotho may participate in a negative regulatory circuit of the vitamin D endocrine system, through the regulation of 1alpha-hydroxylase gene expression...
  31. ncbi Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice
    Shun Ai Li
    Department of Neuroscience, Okayama University Graduate School of Medicine and Dentistry, 2 5 1 Shikata cho, Okayama 700 8558, Japan
    Cell Struct Funct 29:91-9. 2004
    ..Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation, which may explain why mutation of klotho gene results in a variety of phenotypes...
  32. pmc In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis
    Teruyo Nakatani
    Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA 02115, USA
    FASEB J 23:433-41. 2009
    ..Together, these results provide compelling evidence that Fgf23 does not have a klotho-independent role in the regulation of systemic phosphate and vitamin D homeostasis...
  33. ncbi Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane
    Akihiro Imura
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto 606 8501, Japan
    FEBS Lett 565:143-7. 2004
    ..The secreted as well as the membrane-bound Klotho proteins were suggested to form oligomerized complex. These results delineate post-translation processing of Klotho and possible regulatory mechanisms for secretion of Klotho in vivo...
  34. pmc Klotho prevents renal calcium loss
    R Todd Alexander
    Department of Physiology, Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands
    J Am Soc Nephrol 20:2371-9. 2009
    ..This highlights the importance of klotho to the prevention of renal Ca(2+) loss, secondary hypervitaminosis D, osteopenia, and nephrocalcinosis...
  35. ncbi betaKlotho is required for fibroblast growth factor (FGF) 21 signaling through FGF receptor (FGFR) 1c and FGFR3c
    Masashi Suzuki
    Signaling Molecules Research Laboratory, National Institute of Advanced Industrial Science and Technology, Central 6, 1 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
    Mol Endocrinol 22:1006-14. 2008
    ..It is thus suggested that betaKlotho expression is a crucial determinant of the FGF21 specificity of the target cells upon which it acts in an endocrine fashion...
  36. ncbi Circulating α-klotho levels in CKD and relationship to progression
    Hyoung Rae Kim
    Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea
    Am J Kidney Dis 61:899-909. 2013
    ..However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown...
  37. ncbi In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage
    Haruo Mitani
    Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    Hypertension 39:838-43. 2002
    ....
  38. pmc Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse
    Catherine A Brownstein
    Department of Genetics, Yale University School of Medicine, 333 Cedar Street, SHM I 308, New Haven, Connecticut 06510, USA
    Endocrinology 151:492-501. 2010
    ....
  39. pmc Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects
    Yuji Yamazaki
    Antibody Research Laboratories, Kyowa Hakko Kirin Co Ltd, Tokyo 194 8533, Japan
    Biochem Biophys Res Commun 398:513-8. 2010
    ..Although the importance of transmembrane-type alphaKl has been demonstrated, less is known regarding the physiological importance of soluble-type alphaKl (salphaKl) in circulation...
  40. ncbi Liver-specific activities of FGF19 require Klotho beta
    Benjamin C Lin
    Department of Molecular Oncology, Genentech Inc, South San Francisco, CA 94080, USA
    J Biol Chem 282:27277-84. 2007
    ..The tissue-specific activity of FGF19 supports the unique intersection of KLB and FGFR4 distribution in liver. These studies define KLB as a novel FGFR4 coreceptor required for FGF19 liver specific functions...
  41. ncbi Heparanase expression in human colorectal cancer and its relationship to tumor angiogenesis, hematogenous metastasis, and prognosis
    Tomohiro Sato
    First Department of Surgery, University of Fukui, Matsuoka cho, Yoshida gun, Fukui, Japan
    J Surg Oncol 87:174-81. 2004
    ..Heparanase is considered to play an important role in tumor invasion and hematogenous metastasis. The aim of this study was to determine the expression of heparanase in colorectal cancer to evaluate its prognostic value...
  42. pmc Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members
    Regina Goetz
    Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell Biol 27:3417-28. 2007
    ..Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors...
  43. pmc Proteoglycans in health and disease: new concepts for heparanase function in tumor progression and metastasis
    Uri Barash
    Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Haifa, Israel
    FEBS J 277:3890-903. 2010
    Heparanase is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains at a limited number of sites, yielding heparan sulfate fragments of still appreciable size...
  44. ncbi Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer
    I Wolf
    Institute of Oncology Chaim Sheba Medical Center, Ramat Gan, Israel
    Oncogene 27:7094-105. 2008
    ..These data suggest klotho as a potential tumor suppressor and identify it as an inhibitor of the IGF-1 pathway and activator of the FGF pathway in human breast cancer...
  45. pmc Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells
    Liduan Zheng
    Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
    BMC Cancer 10:33. 2010
    ..The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells...
  46. pmc MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase
    Lixin Zhang
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
    Cancer Res 71:645-54. 2011
    ....
  47. pmc T-DNA insertional mutagenesis for activation tagging in rice
    Dong Hoon Jeong
    Department of Life Science and National Research Laboratory of Plant Functional Genomics, Pohang University of Science and Technology, Pohang 790 784, Republic of Korea
    Plant Physiol 130:1636-44. 2002
    ..The binary vector contains the promoterless beta-glucuronidase (GUS) reporter gene next to the right border...
  48. ncbi Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis
    I Vlodavsky
    Department of Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel
    Nat Med 5:793-802. 1999
    ..Cloning of the heparanase gene enables the development of specific molecular probes for early detection and treatment of cancer metastasis and autoimmune disorders...
  49. pmc Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation
    Regina Goetz
    Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 107:407-12. 2010
    ..We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting...
  50. ncbi Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation
    Yoshihiro Maekawa
    Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    Endocrine 35:341-6. 2009
    ..These results suggest that Klotho suppresses TNF-alpha-induced expression of adhesion molecules and NF-kappaB activation. Klotho may have a role in the modulation of endothelial inflammation...
  51. pmc Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mi
    Marco A Passini
    Department of Pathobiology and Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Virol 77:7034-40. 2003
    ..The number of cells positive for a vector-encoded secreted enzyme (beta-glucuronidase) was notably greater and more widespread in AAV1-injected brains...
  52. ncbi The Klotho gene family as a regulator of endocrine fibroblast growth factors
    Hiroshi Kurosu
    Department of Hygiene and Public Health I, Tokyo Women s Medical University, 8 1, Kawada cho, Shinjuku ku, Tokyo 162 8666, Japan
    Mol Cell Endocrinol 299:72-8. 2009
    ..This review summarizes recent progress in understanding of Klotho and betaKlotho function in the regulation of tissue-specific metabolic activity of the endocrine fibroblast growth factors (FGF19, FGF21, and FGF23)...
  53. pmc Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase
    Mutsuko Ohnishi
    Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA
    Kidney Int 75:1166-72. 2009
    Changes in the expression of klotho, a beta-glucuronidase, contribute to the development of features that resemble those of premature aging, as well as chronic renal failure...
  54. pmc Relevant use of Klotho in FGF19 subfamily signaling system in vivo
    Ken ichi Tomiyama
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 107:1666-71. 2010
    ..One-to-one functional interactions such as alpha-Klotho/FGF23, beta-Klotho/FGF15 (humanFGF19), and undefined cofactor/FGF21 would result in tissue-specific signal transduction of the FGF19 subfamily...
  55. pmc Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity
    Tetsuro Kusaba
    Department of Cardiovascular and Renal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602 8566, Japan
    Proc Natl Acad Sci U S A 107:19308-13. 2010
    ..These findings provide evidence that Klotho protein is associated with VEGFR-2/TRPC-1 in causing cointernalization, thus regulating TRPC-1-mediated Ca(2+) entry to maintain endothelial integrity...
  56. ncbi A new targeting approach for breast cancer gene therapy using the heparanase promoter
    Martina Breidenbach
    Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, 901 19th Street South, BMR2 508, University of Alabama at Birmingham, Birmingham, AL 35294 2172, USA
    Cancer Lett 240:114-22. 2006
    ..We conclude that the HPR pathway is a promising target for the development of breast cancer directed gene therapy strategies...
  57. pmc Heparanase activity in alveolar and embryonal rhabdomyosarcoma: implications for tumor invasion
    Valentina Masola
    Department of Experimental Biomedical Sciences, University of Padova, 35121 Padova, Italy
    BMC Cancer 9:304. 2009
    ..This feature is influenced by several biological molecules, including soluble factors secreted by tumor cells, such as heparanase (HPSE). HPSE is an endo-beta-D-glucuronidase that cleaves heparan sulphate proteoglycans.
  58. pmc Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging
    Mutsuko Ohnishi
    Department of Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA
    FASEB J 24:3562-71. 2010
    ..The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging...
  59. ncbi Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70
    Hidekazu Sugiura
    Department of Medicine IV, Tokyo Women s Medical University, Tokyo, Japan
    Nephrol Dial Transplant 25:60-8. 2010
    ....
  60. ncbi Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases
    R Nagai
    Second Department of Internal Medicine, Gunma University School of Medicine, Japan
    Cell Mol Life Sci 57:738-46. 2000
    ..The Klotho protein itself, or its metabolites, promotes endothelial NO production in aorta as well as arterioles, and klotho mRNA in kidney is downregulated under sustained circulatory stress...
  61. ncbi Serum soluble α-klotho in hemodialysis patients
    Keitaro Yokoyama
    Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
    Clin Nephrol 77:347-51. 2012
    ..The extracellular domain of klotho is cleaved and released into various extracellular fluids, such as blood, urine, and cerebrospinal fluid, as soluble α-klotho (sαKl)...
  62. ncbi The role of glycosylation and phosphorylation in the expression of active human beta-glucuronidase
    J M Shipley
    Edward A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, Missouri 63104
    J Biol Chem 268:12193-8. 1993
    ..site-directed mutagenesis to observe the effect of eliminating selective glycosylation sites from human beta-glucuronidase on enzyme sorting...
  63. pmc Plasma klotho and cardiovascular disease in adults
    Richard D Semba
    Department of Ophthalmology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA
    J Am Geriatr Soc 59:1596-601. 2011
    ..To determine whether plasma klotho, a recently discovered hormone that has been implicated in atherosclerosis, is related to prevalent cardiovascular disease (CVD) in adults...
  64. ncbi Validation of an immunoassay for soluble Klotho protein: decreased levels in diabetes and increased levels in chronic kidney disease
    Sridevi Devaraj
    Department of Pathology and Immunology, Texas Children s Hospital and Baylor College of Medicine, Houston, USA
    Am J Clin Pathol 137:479-85. 2012
    ..5%; P < .001). We also documented significantly higher levels of Klotho with CKD. Thus, we validated an assay for Klotho and made the novel observation that levels are decreased in diabetes and increased in CKD...
  65. pmc Klotho lacks a vitamin D independent physiological role in glucose homeostasis, bone turnover, and steady-state PTH secretion in vivo
    René Anour
    Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria
    PLoS ONE 7:e31376. 2012
    ..In conclusion, our findings cast doubt on a physiologically relevant vitamin D and Fgf23 independent function of Klotho in the regulation of glucose metabolism, bone turnover, and steady-state PTH secretion in vivo...
  66. ncbi Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells
    J Ray
    James A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA
    Genomics 48:248-53. 1998
    ..VII (MPS VII) is an inherited disease resulting from deficient activity of the lysosomal acid hydrolase beta-glucuronidase (GUSB) and has been reported in humans, mice, cats, and dogs...
  67. ncbi Reduced Klotho expression level in kidney aggravates renal interstitial fibrosis
    Hidekazu Sugiura
    Dept of Medicine IV, Tokyo Women s Medical Univ, 8 1 Kawada cho, Shinjuku City, Tokyo, Japan 162 8666
    Am J Physiol Renal Physiol 302:F1252-64. 2012
    ..Taken together, renal fibrosis can trigger a deterioration spiral of Klotho expression, which may be involved in the pathophysiology of CKD progression...
  68. ncbi Decreased renal α-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion
    Osamu Asai
    First Department of Internal Medicine, Nara Medical University, Kashihara, Japan
    Kidney Int 81:539-47. 2012
    ..Thus, α-Klotho expression was decreased in distal convoluted tubules in diabetic nephropathy in humans and mice. Renal loss of α-Klotho may affect urinary calcium excretion in early diabetic nephropathy...
  69. pmc An artificial miRNA against HPSE suppresses melanoma invasion properties, correlating with a down-regulation of chemokines and MAPK phosphorylation
    Xiaoyan Liu
    Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People s Republic of China
    PLoS ONE 7:e38659. 2012
    ..Furthermore, miRNA-based RNAi was also a powerful tool for gene function study...
  70. ncbi Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A
    Ina Maria Kacso
    University of Medicine and Pharmacy Iuliu Hatieganu Cluj Napoca, Department of Nephrology, Romania
    Clin Biochem 45:1415-20. 2012
    ..Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A)...
  71. ncbi Klotho expression in epithelial ovarian cancer and its association with insulin-like growth factors and disease progression
    Lingeng Lu
    Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520 8034, USA
    Cancer Invest 26:185-92. 2008
    ..In conclusion, Klotho expression is associated with epithelial ovarian cancer progression, and the protein may serve as an independent marker for ovarian cancer prognosis. Klotho's role in cancer warrants further elucidation...
  72. pmc A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease
    Masashi Kitagawa
    Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    PLoS ONE 8:e56695. 2013
    ..However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD)...
  73. pmc Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease
    Tetsu Akimoto
    Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311 1 Yakushiji, Shimotsuke shi, Tochigi, 329 0498, Japan
    BMC Nephrol 13:155. 2012
    ..The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD)...
  74. ncbi Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study
    Ivana Pavik
    Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland
    Nephrol Dial Transplant 28:352-9. 2013
    ..FGF23 levels have been shown to increase early in chronic kidney disease (CKD); however, the corresponding soluble Klotho levels at the different CKD stages are not known...
  75. ncbi Urinary heparanase activity in patients with Type 1 and Type 2 diabetes
    Angelique L W M M Rops
    Nephrology Research Laboratory, Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nephrol Dial Transplant 27:2853-61. 2012
    ....
  76. pmc Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism
    Hannes Olauson
    Clinical Research Center, Sixth Floor, Novumhuset, Karolinska University Hospital in Huddinge, Stockholm, Sweden
    J Am Soc Nephrol 23:1641-51. 2012
    ..Taken together, renal FGF23-Klotho signaling, which is disrupted in CKD, is essential for homeostatic control of mineral metabolism...
  77. pmc Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression
    Miry Blich
    Department of Cardiology and Pathology, Rambam Health Care Campus, Haifa, Israel
    Arterioscler Thromb Vasc Biol 33:e56-65. 2013
    ..Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages...
  78. ncbi Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys
    Y Kato
    Tokyo Research Laboratories, Kyowa Hakko Kogyo Co Ltd, 3 6 6, Asahi machi, Machida shi, Tokyo, 194 8533, Japan
    Biochem Biophys Res Commun 267:597-602. 2000
    ..The mAbs established in this paper will serve as useful analytical, pathological, and diagnostic tools to disclose the role of Klotho protein in the suppression of a syndrome resembling human aging...
  79. pmc Soluble klotho and autosomal dominant polycystic kidney disease
    Ivana Pavik
    Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland
    Clin J Am Soc Nephrol 7:248-57. 2012
    ..This study explored potential mechanisms underlying resistance to FGF23 in ADPKD...
  80. pmc Heparanase 2 interacts with heparan sulfate with high affinity and inhibits heparanase activity
    Flonia Levy-Adam
    Cancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
    J Biol Chem 285:28010-9. 2010
    ..03). Hpa2 appears to restrain tumor metastasis, likely by attenuating heparanase enzymatic activity, conferring a favorable outcome of head and neck cancer patients...
  81. ncbi The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel
    Q Chang
    Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands
    Science 310:490-3. 2005
    ..We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a beta-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane...
  82. ncbi Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies
    O Ostrovsky
    Laboratory of Molecular Immunobiology, Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
    Leukemia 21:2296-303. 2007
    Heparanase, endo-beta-D-glucuronidase, degrades heparan sulfate glycosaminoglycans - the principal polysaccharide of the basement membrane and extracellular matrix...
  83. pmc Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity
    Vishnu C Ramani
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2182, USA
    J Biol Chem 286:6490-9. 2011
    ..This work also provides further mechanistic insight into the dynamic role of heparanase in driving aggressive tumor progression...
  84. ncbi Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein
    T Shiraki-Iida
    Division of Molecular Genetics, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan
    FEBS Lett 424:6-10. 1998
    ..These findings provide fundamental information for further study of the kl gene which may regulate aging in vivo...
  85. ncbi Mammalian heparanase: what is the message?
    Veronique Vreys
    Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium
    J Cell Mol Med 11:427-52. 2007
    ..In that context, we also briefly discuss heparanase-2, an intriguing close homologue of heparanase-1, for which, so far, no heparan sulphate-degrading activity could be demonstrated...
  86. ncbi Faecal microflora and beta-glucuronidase expression are altered in an irinotecan-induced diarrhea model in rats
    Andrea M Stringer
    Department of Medical Oncology, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia
    Cancer Biol Ther 7:1919-25. 2008
    ..However, the pathophysiology behind this debilitating side effect remains unclear. Irinotecan causes cholinergic and delayed onset diarrhea in patients, in which beta-glucuronidase produced by gut bacteria is thought to be involved.
  87. pmc Murine mucopolysaccharidosis type VII. Characterization of a mouse with beta-glucuronidase deficiency
    E H Birkenmeier
    Jackson Laboratory, Bar Harbor, Maine 04609
    J Clin Invest 83:1258-66. 1989
    We have characterized a new mutant mouse that has virtually no beta-glucuronidase activity...
  88. pmc Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma
    Weijie Poh
    Department of Pharmacy, National University of Singapore, Singapore
    Mol Cancer 11:14. 2012
    ..Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression...
  89. ncbi Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer
    Jie Pan
    Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Tumour Biol 32:729-35. 2011
    ..Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC...
  90. ncbi Alteration of microRNA expression in the process of mouse brain growth
    Akiko Eda
    National Institute of Neuroscience, NCNP, Ogawahigashi, Kodaira, Tokyo, Japan
    Gene 485:46-52. 2011
    ....
  91. ncbi Heparanase induces tissue factor pathway inhibitor expression and extracellular accumulation in endothelial and tumor cells
    Yona Nadir
    Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
    Thromb Haemost 99:133-41. 2008
    ....
  92. ncbi Vascular deconjugation of quercetin glucuronide: the flavonoid paradox revealed?
    Carmen Menendez
    Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain
    Mol Nutr Food Res 55:1780-90. 2011
    ..We aimed to determine whether glucuronidated quercetin can deconjugate in situ and whether deconjugation leads to a biological effect...
  93. ncbi Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting
    Annamaria Naggi
    G Ronzoni Institute for Chemical and Biochemical Research, Via G Colombo, 81, 20133 Milan, Italy
    J Biol Chem 280:12103-13. 2005
    Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate (HS) chains of heparan sulfate proteoglycans on cell surfaces and in the extracellular matrix (ECM)...
  94. ncbi The FRUITFULL MADS-box gene mediates cell differentiation during Arabidopsis fruit development
    Q Gu
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Development 125:1509-17. 1998
    ..beta-glucuronidase (GUS) reporter gene expression in the enhancer trap line is observed specifically in all cell layers of the ..
  95. pmc Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process
    Mohammed S Razzaque
    Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts 02115, USA
    FASEB J 20:720-2. 2006
    ..Finally, our data support a new model of interactions among Fgf-23, vitamin D, and klotho, a gene described as being associated with premature aging process...
  96. pmc The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging
    C C Hsieh
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Aging (Albany NY) 2:597-611. 2010
    ..activating ASK1-signalosomes. We conclude that the Klotho suppressor-of-aging activity is linked to the ASK1-signalsome, a physiological ROS-sensitive signaling center...
  97. ncbi Heparanase involvement in physiology and disease
    N J Nasser
    Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel
    Cell Mol Life Sci 65:1706-15. 2008
    ..Heparanase overexpression in a variety of malignant tumors suggests that it could be a target for anti-cancer therapy...
  98. pmc SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the heparanase/syndecan-1 axis
    Joseph P Ritchie
    Department of Pathology, Center for Metabolic Bone Disease, and Comprehensive Cancer Center, University of Alabama at Birmingham, Alabama 35294, USA
    Clin Cancer Res 17:1382-93. 2011
    ..SST0001, a nonanticoagulant heparin with antiheparanase activity, was examined for its inhibition of myeloma tumor growth in vivo and for its mechanism of action...
  99. ncbi Heparanase promotes growth, angiogenesis and survival of primary breast tumors
    Irit Cohen
    Department of Oncology, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Int J Cancer 118:1609-17. 2006
    ..Our results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival...
  100. pmc Alternatively spliced Spalax heparanase inhibits extracellular matrix degradation, tumor growth, and metastasis
    Nicola J Nasser
    Department of Oncology, Shaare Zedek Medical Center, Jerusalem 91031, Israel
    Proc Natl Acad Sci U S A 106:2253-8. 2009
    ....
  101. ncbi The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc
    K Morishita
    Tsukuba Research Laboratories, Kyowa Hakko Kogyo Company Limited, Tsukuba-shi, Ibaraki 305-0841, Japan
    J Nutr 131:3182-8. 2001
    ..05). These results indicate that dietary phosphorus and zinc modulate the phenotypes of klotho mice, and that klotho expression in the kidneys is regulated not only in klotho mutant mice, but also in wild-type mice...

Research Grants65

  1. Gene Therapy of Mucopolysaccharidosis VII
    Mark E Haskins; Fiscal Year: 2012
    Mucopolysaccharidosis VII (MPS VII) is a rare lysosomal storage disease caused by deficient [unreadable]-glucuronidase (GUSB) activity, resulting in the accumulation of glycosaminoglycans (GAG)...
  2. Using vitamin D glucuronide pro-drugs to prevent/treat colon cancer
    JESSE PAUL GOFF; Fiscal Year: 2013
    ..Upon reaching the lower intestinal tract, however, [unreadable]-glucuronidase enzymes produced by resident bacterial populations cleave off the glucuronide and release the active hormone...
  3. RECEPTOR-MEDIATED TRANSPORT OF LYSOSOMAL ENZYMES
    William S Sly; Fiscal Year: 2013
    ..We will use 2- glucuronidase and 1-iduronidase as model enzymes and murine mucopolysaccharidosis type VII (MPS VII;Sly disease) and MPS I (..
  4. ALIMENTARY TRACT LIPIDS IN HEALTH AND DISEASE
    MARTIN CONRAD CAREY; Fiscal Year: 2013
    ..linked cholic acid, a strong bilirubin binder, or 13-glucaro,l-4 lactone, a potent inhibitor of bacterial 6-glucuronidase. iv) Aim four will work out, both experimentally and by molecular dynamic simulations, the physical states of ..
  5. PATHOGENESIS OF DISEASE IN MUCOPOLYSACCHARIDOSIS I AND VII
    Katherine P Ponder; Fiscal Year: 2010
    ..diseases in which glycosaminoglycans (GAG) accumulate due to deficient activity in a-Liduronidase and b-glucuronidase, respectively. This results in multisysten, which are very important for their structural integrity...
  6. SB Transposons for Gene Therapy
    Perry B Hackett; Fiscal Year: 2013
    ..In the past few years we have demonstrated our ability to deliver both 2-glucuronidase (GUSB) and a-L-iduronidase (IDUA) encoding genes to mouse liver and thereby correct accumulation of storage ..
  7. Organ-specific Ugt1 profiling in detoxifying the anticancer drug CPT-11
    Shujuan Chen; Fiscal Year: 2013
    ..via the biliary ducts into the gastrointestinal (GI) tract, where it serves as a substrate for bacterial ?-glucuronidase enzymes produced by microflora...
  8. Development of Novel Drugs to Alleviate CPT-11 Toxicity
    Matthew R Redinbo; Fiscal Year: 2013
    ..the in situ production of the active metabolite, SN- 38, from inactive SN-38-glucuronde by microbial ?-glucuronidase residing within the gut lumen. We recently elucidated the crystal structure of E...
  9. Improving CPT-11 Efficacy Using Structural and Chemical Biology
    Matthew R Redinbo; Fiscal Year: 2013
    ..We have shown in preliminary studies that such compounds specifically disrupt b-glucuronidase activity with mM to sub- nM potency in Gram-positive and Gram-negative bacteria grown under aerobic and ..
  10. MOLECULAR ANALYSIS OF FLOWERING GENES OF PHARBITIS NIL
    Anath Das; Fiscal Year: 1991
    ..g. E. Coli beta-glucuronidase, GUS) will be constructed...
  11. GENE TRANSFER TO AND EXPRESSION IN NEURONS IN VIVO
    NIGEL WILLIAM FRASER; Fiscal Year: 2013
    ..Specifically, we have used a [unreadable]-glucuronidase (GUSB) negative mouse (gusmps/gusmps), with mucopolysaccharidosis (MPS) type VII (Sly disease), as an animal ..
  12. Peptides surface modification to prevent stent blockage
    Joseph Leung; Fiscal Year: 2006
    ..Biliary sludge formed as a result of deconjugation of bilirubin diglucuronide by bacterial Beta-glucuronidase, resulting in the precipitation of calcium bilirubinate...
  13. NONSENSE RNA SURVEILLANCE IN HEALTH AND DISEASE
    Harry Dietz; Fiscal Year: 2000
    ..will use a spontaneous frameshift mutation known as gusmps which causes a 200-fold decrease in murine beta-glucuronidase mRNA levels...
  14. IN UTERO GENE THERAPY
    John Wolfe; Fiscal Year: 2005
    ..Animal models with Beta-glucuronidase (GUSB) deficiency, causing mucopolysaccharidosis (MPS) VII (Sly disease), will be studied...
  15. BOTANICAL/DRUG INTERACTIONS IN HIV: GLUCURONIDATION
    Philip Smith; Fiscal Year: 2004
    ..The internal lactone form of glucarate is a well-known, widely used inhibitor of beta-glucuronidase. Piperine and silybin are potent and broad inhibitor of glucuronidation and can also inhibit oxidative enzyme ..
  16. ADENO-ASSOCIATED VIRUS GENE TRANSFER INTO NEONATES
    Mark Sands; Fiscal Year: 1999
    ..novel AAV vectors for use in the lysosomal storage disease mucopolysaccharidosis type VII (MPS VII, beta-glucuronidase deficiency)...
  17. Glucuronidation in Humans--Genotypes and Phenotypes
    Johanna Lampe; Fiscal Year: 2004
    ..The opposite reaction, the hydrolysis of such glucuronide moieties by human beta-glucuronidase (f3-G) can restore biologic activity of xenobiotics and steroid hormones...
  18. PRE-IMPLANTATION DIAGNOSIS OF GENETIC DISEASE
    James Goldberg; Fiscal Year: 1990
    ..This proposal is to develop pre-implantation embryonic biopsy techniques in beta-glucuronidase deficient mice...
  19. TRANSPLANTATION OF NEURAL PROGENITOR CELLS
    GREGORY HEUER; Fiscal Year: 2002
    ..Deficiencies in the gene encoding he lysosomal enzyme -glucuronidase (GUSB) result in Sly disease or MPS type VII (MPS VII)...
  20. THERAPY OF GENETIC DISEASES
    ROBERT DESNICK; Fiscal Year: 1980
    ..isolated hepatocytes from normal mice will be administered intraportally to congenic mice with defective Beta-glucuronidase activity; the ability of these hepatocellular allografts to produce normal enzyme will be evaluated...
  21. PROSTAGLANDIN BIOSYNTHESIS IN LUNG MACROPHAGES
    Wei Hsueh; Fiscal Year: 1980
    Rabbit alveolar macrophages secrete lysosomal enzymes (such as acid phosphatase and beta-glucuronidase), arachidonic acid, and prostaglandins (PGs) during zymosan phagocytosis...
  22. ANDORGENS IN REPRODUCTION: PRODUCTION AND ACTION
    CLYDE BARDIN; Fiscal Year: 1980
    Androgens stimulate the rate of beta-glucuronidase synthesis in mouse kidney...
  23. COMPREHENSIVE GENE THERAPY FOR MUCOPOLYSACCHARIDOSIS VII
    Jayanta Roy Chowdhury; Fiscal Year: 2009
    ..In this project, we will target mucopolysaccharidosis-VTI (MPS-VII, beta-glucuronidase deficiency, Sly syndrome), since a well-characterized murine model is available...
  24. GLYCOSAMINOGLYCAN EFFECT ON ARTERIAL SMOOTH MUSCLE CELLS
    Samuel Smith; Fiscal Year: 1990
    ..differences in glycosaminoglycan (chondroitin-6-sulfate) accumulation and intracellular distribution of B-glucuronidase (greater localization in endoplasmic reticulum) precede cholesteryl ester accretion in lesion-prone areas of ..
  25. GENE THERAPY FOR LYSOSOMAL STORAGE DISEASE
    Gordon Watson; Fiscal Year: 2002
    ..MPS) type VII, or Sly syndrome, is a lysosomal storage disease that develops when there is insufficient beta-glucuronidase (GUS) to aid in the breakdown of glycosaminoglycans...
  26. AIRWAY MYOCYTE PROLIFERATION AND LYSOSOMAL HYDROLASE
    DUKHEE LEW; Fiscal Year: 2001
    ..action of mannosyl-rich glycoproteins including lysosomal hydrolases (beta-hexosaminidase A & B and beta-glucuronidase) on bovine airway smooth muscle cells...
  27. MPS VII TREATMENT USING AAV4 AND AAV5 VECTORS
    Jason Heth; Fiscal Year: 2000
    ..VII(MPS VII) is a representative LSD characterized by absent or severely decreased levels of B-glucuronidase, with both CNS and systemic involvement...
  28. Phenotypic Determinants of Murine Cholelithiasis
    Martin Carey; Fiscal Year: 2004
    ..As a result of a more acidic bile, there will be increased endogenous ?-glucuronidase activity intrahepatically, as well as in the gallbladder, with augmented hydrolysis of bilirubin conjugates ..
  29. FUNCTIONAL STUDIES OF MPS VII MICE AFTER ENZYME THERAPY
    Mark Sands; Fiscal Year: 2000
    ..We demonstrated that intravenous injections of phosphorylated beta-glucuronidase started at birth resulted in relatively high levels of enzyme in the brain...
  30. MPS VII CNS Gene Therapy Using Neuronal Stem Cells
    Kyuson Yun; Fiscal Year: 2007
    ..The Mucopolysaccharidosis Type VII (MRS VII) mouse, lacking the lysosomal enzyme beta-glucuronidase (GUS), is uniquely suited to these goals because of the well-characterized CNS involvement...
  31. EFFECTS OF AGING ON OVULATED EGGS AND FERTILIZATION
    Frank Longo; Fiscal Year: 1980
    ..g., carbohydrates and enzymes (acid and alkaline phosphastases, nucleosides triphosphatase and beta-glucuronidase) will be carried out...
  32. AAV correction of CNS deficits in an MPS model of LSD
    Beverly Davidson; Fiscal Year: 2007
    ..Representative of the LSDs are the mucopolysaccharidoses (MPS), and specifically, I&-glucuronidase deficiency or MPS VII. As yet, systemic treatments for the MPS have no effect on CNS involvement...
  33. FINAL EXPRESSION OF BETA-GLUCURONIDASE IN DROSOPHILA
    Daniel Hartl; Fiscal Year: 1980
    ..The overall objectives of the project are to understand the genetic basis and regulation of the enzyme beta-glucuronidase in Drosophila and to determine its metabolic role...
  34. MODEL RESOURCE FOR HUMAN INHERITED DISEASES
    Philip Wood; Fiscal Year: 1990
    ..have begun to develop a mouse model of choice using antisense RNA techniques to block synthesis of mouse B-glucuronidase in cultured cells and eventually in transgenic mice...
  35. MABZYMES TO ACTIVATE ANTICANCER GLUCURONIDE PRODRUGS
    JAMES LARRICK; Fiscal Year: 1993
    ..associated with chemoimmunoconjugates we prepared an enzyme-MAB conjugate (MABzyme) by chemically linking beta-glucuronidase to an anti- hepatoma MAB...
  36. STRATEGIES TO ENHANCE GENE TRANSFER TO THE CNS
    Beverly Davidson; Fiscal Year: 2009
    ..We will use the beta-glucuronidase deficient (MPS VII) mouse as a model of progressive CNS lysosomal storage disease to address our questions...
  37. PERIODONTITIS IN STRESSED ALZHEIMER CAREGIVERS
    Theresa Madden; Fiscal Year: 1993
    ..depth, clinical attachment level, bleeding index, and gingival crevicular fluid concentrations of PGE2 and b-glucuronidase between groups will be made...
  38. HUMAN PMN LYSOSOME INDUCTION IN AGGRESSIVE PERIODONTITIS
    DAVID PIPPIN; Fiscal Year: 1990
    ..of lysosomal enzymes and amounts secreted at FMLP challenge will be monitored by colorimetric assay for beta-glucuronidase, a characteristic lysosomal enzyme...
  39. NEUROTROPHINS AND MALIGNANT MELANOMA
    Dario Marchetti; Fiscal Year: 1999
    ..Matrigel), c) time- and dose-dependent induction of heparanase, a heparan sulfate specific endo-beta-D-glucuronidase associated with human melanoma metastasis and d) increased cellular invasion in a chemoinvasion assay ..
  40. PRODUCTION OF BETA-GLUCURONIDASE FOR MPS VII
    Emil Kakkis; Fiscal Year: 2002
    ..PROPOSED COMMERCIAL APPLICATION: The enzyme and process created from this work can be used to produce enzyme and treat patients suffering from Mucopolysaccharidosis VII, a serious, life-threatening genetic disorder. ..
  41. LENTIVIRAL VECTOR GENE TRANSFER TO THE CNS IN MPS VII
    Deborah Watson; Fiscal Year: 2000
    ..One of these diseases, MPS VII, is caused by a lack of the lysosomal enzyme beta- glucuronidase (GUSB)...
  42. AAV-mediated Gene Targeting in the Retina
    NADINE DEJNEKA; Fiscal Year: 2004
    ..Experiments will subsequently be performed in beta-glucuronidase- deficient mice (gusmps/gusmps)...
  43. ATTACHMENT OF RIBOSOMES TO MICROSOMAL MEMBRANES
    David Sabatini; Fiscal Year: 1991
    ..2) The identification of structural features in beta- glucuronidase responsible for the phosphorylation of the mannose residues that determine the sequestration of this protein ..
  44. DOMINANT PEPTIDE INHIBITORS OF PLANT VIRUS REPLICATION
    Robert Sandrock; Fiscal Year: 2001
    ..from these tobacco cells will be infected with transcripts of TEV that has been modified to include the b-glucuronidase (GUS) gene in its genome. The impact of these peptides on TEV replication will be monitored by GUS activity...
  45. FINAL EXPRESSION OF BETA-GLUCURONIDASE IN DROSOPHILA
    Victoria Finnerty; Fiscal Year: 1980
    ..We propose to investigate Beta-glucuronidase in Drosophila as a model for the genetic analysis of such regulation...
  46. SYNTHESIS AND APPLICATIONS OF FLUORESCENT SUBSTRATES
    Richard Haugland; Fiscal Year: 1990
    ..substrates and novel included are new substrates that can detect single lacZ beta-galactosidase or GUS beta-glucuronidase transfected cells through development of a improved fluorescent substrates for detection and innovative ..
  47. TUMOR BASEMENT MEMBRANE DEGRADING ENZYMES
    Garth Nicolson; Fiscal Year: 1991
    ..The results from these studies should provide new information concerning the mechanisms of tumor cell invasion at the molecular level, and allow development of new approaches of diagnosis or prognosis of metastasis...
  48. STEM CELL MOBILIZATION TO ENHANCE TISSUE REGENERATION
    Daniel Link; Fiscal Year: 2006
    ..These mice are deficient in b-glucuronidase (GUSB), a ubiquitously expressed lysosomal enzyme...
  49. CHLORIDE TRANSPORT REGULATORY HORMONES IN MAN
    CHARLES WATLINGTON; Fiscal Year: 1980
    ..Also, the activity in urine is enhanced by glucuronidase - sulfatase hydrolysis...
  50. AAV-mediated gene correction in retina
    Jean Bennett; Fiscal Year: 2007
    ..Experiments will subsequently be performed in beta- glucuronidase- deficient mice (gusmps/gusmps)...
  51. Proteomics of mouse models for aging and longevity
    Makoto Kuro O; Fiscal Year: 2008
    ..These studies are expected to provide critical information that promotes a better understanding of the molecular mechanisms of aging and longevity. [unreadable] [unreadable]..
  52. ADJUNCT VITAMIN A THERAPY FOR TUBERCULOSIS AND HIV/AIDS
    Richard Semba; Fiscal Year: 2005
    ....
  53. MICRONUTRIENTS AND MOTHER TO CHILD TRANSMISSION OF HIV
    Richard Semba; Fiscal Year: 2001
    ..The relationship between mastitis and breastmilk HIV load and the epidemiology and microbiology of mastitis will be examined in a new cohort of HIV-infected lactating women. ..
  54. VITAMIN A SUPPLEMENTATION FOR HIV INFECTED CHILDREN
    Richard Semba; Fiscal Year: 2002
    ....
  55. Iron Deficiency and Anemia in HIV and HCV-Infected Women
    Richard Semba; Fiscal Year: 2005
    ..S. and elsewhere. ..
  56. Hepcidin and the pathogenesis of anemia in older adults.
    Richard D Semba; Fiscal Year: 2010
    ..This study should provide new insight into the epidemiology and biological mechanisms of anemia among older adults and help identify strategies aimed at the prevention and treatment of anemia. ..
  57. Oxidative Stress and the Pathogenesis of Sarcopenia and Disability in Older Women
    Richard Semba; Fiscal Year: 2008
    ..AGEs are a potentially modifiable risk factor, as circulating AGEs can be lowered by dietary modification and by pharmacological intervention. ..
  58. CHARACTERIZATION AND TREATMENT OF MURINE MPS VII
    Brian Soper; Fiscal Year: 2006
    ..The lysosomal enzyme, beta-glucuronidase (GUSB), involved in degradation of glycosaminoglycans (GAG's) is absent in MPS VII...
  59. INVERSE METASTATIC MODALITIES BY HEPARANASES
    Dario Marchetti; Fiscal Year: 2005
    ..They will provide a framework for the development of polysaccharide-based anti-cancer molecules as important prognostic tools and diagnostic screens for metastatic detection, diagnosis and treatment. ..
  60. GENETIC ENGINEERING OF CELLS FROM ANEMIC ANIMALS
    Jane Barker; Fiscal Year: 2003
    ..While the beta-glucuronidase (beta-GUS) deficiency in MPS VII can be cross-corrected post-myeloablation by tissue macrophages from donor +/+..
  61. FACSVantage SE Sorting Flow Cytometer
    Jane Barker; Fiscal Year: 2002
    ..Funds are requested to purchase the FACSVantage SE and the optional equipment for TJL's Flow Cytometry Service. This will provide a cost-effective way to fill an urgent need of TJL's principal investigators. ..
  62. STUDENT PARTNERS IN CANCER RESEARCH AND EDUCATION
    Thomas Kelly; Fiscal Year: 2004
    ..Overall, these students will be able to communicate the importance of cancer detection, prevention, and appropriate treatment in their professional and every-day personal lives, regardless of their eventual specialization or practice. ..