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Gene Review

Hpse  -  heparanase

Rattus norvegicus

Synonyms: Endo-glucoronidase, Hep, Heparanase, Hpa
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Disease relevance of Hpse

  • BACKGROUND: The beta-d-endoglycosidase, heparanase, is emerging as an important contributor to the pathogenesis of proteinuria [1].
  • The purpose of the present study therefore was to examine the role of heparanase in a model of accelerated anti-glomerular basement disease (anti-GBM) [1].
  • A previously validated anti-heparanase antibody associated with proteinuria reduction, in a model of membranous nephropathy, was administered prior to disease induction to establish its impact on protein excretion in this model [1].
  • In both hepatomas, studies using the isoschizomeric pair of restriction enzymes Msp I and Hpa II have indicated hypermethylation of a cytosine residue within or proximal to the hp22 gene [2].
  • These tumor-elicited PMNs (tcPMNs) secrete high levels of the basement-membrane-degrading enzymes, type IV collagenase and heparanase, suggesting that metastatic tumor cells stimulate neutrophilia so that the tcPMNs might assist tumor cell extravasation during metastasis [3].

High impact information on Hpse

  • Two glucose transporter isoforms are expressed in fat cells: (1) the insulin-responsive species which is found only in fat and muscle, and (2) a species corresponding to the erythrocyte/Hep G2/rat brain transporter [4].
  • The effects of insulin and tolazamide on transporter gene expression were studied with probes derived from Hep G2 glucose transporter cDNA [5].
  • The ability of chemically modified heparins to inhibit these immune reactions was associated with their ability to inhibit expression of T lymphocyte heparanase [6].
  • In addition, these cells concomitantly lose expression of the hepatocyte protein Hep-par [7].
  • The extent of methylation of 18 sites in the PEPCK gene in adult liver, kidney, spleen, and heart muscle and in fetal liver has been analyzed using the 5-methylcytosine sensitive enzymes Hpa II and Hha I [8].

Chemical compound and disease context of Hpse


Biological context of Hpse

  • Activity binds to, and is affected by, molecules known to interact with FERM domains, supporting the hypothesis that the intracellular C1A heparanase is the purified FERM domain protein [14].
  • Analysis of EcoRI fragments of DNA from the tumor and control cells after digestion with Hpa II or Msp I endonuclease indicated that the 5'-C-C-G-G-3' sequences in most of the amplified rRNA genes were methylated [15].
  • The P3 promoter was able to drive the expression of a luciferase reporter gene in cell lines Hep G2, PLC/PRF/5, and BHK-21 [16].
  • A cDNA library from the human hepatoma cell line Hep G2 was prepared in the expression vector lambda gt11 [17].
  • The methylation of one single Hpa II site, located in the promoter region, showed particularly strong correlation with the transcriptional activity [18].

Anatomical context of Hpse


Associations of Hpse with chemical compounds

  • Further elucidation of the roles of heparanase in normal physiological processes would provide an important tool for analyzing the regulation of heparan sulfate-dependent cell functions [19].
  • We show here that fat cells isolated from streptozotocin diabetic rats and from fasted rats show a significant (60-80%) decrease in the amount of immunologically detectable insulin-sensitive glucose transporter and no change in the level of the Hep G2/rat brain transporter [4].
  • Accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by Hep G2 was shown to be an active process, being inhibited by low temperature and by the metabolic inhibitor 2,4-dinitrophenol [21].
  • Employing pCPS2.1, a minigene containing the promoter and part of exon 1, we show that nuclear extracts from Hep G2 support accurate carbamyl-phosphate synthetase I gene transcription in vitro [22].
  • A 640-base pair insert spanning +31 to -609 directs expression of the reporter gene chloramphenicol acetyltransferase in an orientation-specific manner in transfected Hep G2 cells [23].

Other interactions of Hpse


Analytical, diagnostic and therapeutic context of Hpse


  1. Heparanase inhibition reduces proteinuria in a model of accelerated anti-glomerular basement membrane antibody disease. Levidiotis, V., Freeman, C., Tikellis, C., Cooper, M.E., Power, D.A. Nephrology (Carlton, Vic.) (2005) [Pubmed]
  2. Covalent modification and repressed transcription of a gene in hepatoma cells. Nakhasi, H.L., Lynch, K.R., Dolan, K.P., Unterman, R.D., Feigelson, P. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  3. Tumor-elicited polymorphonuclear cells, in contrast to "normal" circulating polymorphonuclear cells, stimulate invasive and metastatic potentials of rat mammary adenocarcinoma cells. Welch, D.R., Schissel, D.J., Howrey, R.P., Aeed, P.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  4. Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. Berger, J., Biswas, C., Vicario, P.P., Strout, H.V., Saperstein, R., Pilch, P.F. Nature (1989) [Pubmed]
  5. Coordinate regulation of glucose transporter function, number, and gene expression by insulin and sulfonylureas in L6 rat skeletal muscle cells. Wang, P.H., Moller, D., Flier, J.S., Nayak, R.C., Smith, R.J. J. Clin. Invest. (1989) [Pubmed]
  6. Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins. Lider, O., Baharav, E., Mekori, Y.A., Miller, T., Naparstek, Y., Vlodavsky, I., Cohen, I.R. J. Clin. Invest. (1989) [Pubmed]
  7. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Yang, L., Li, S., Hatch, H., Ahrens, K., Cornelius, J.G., Petersen, B.E., Peck, A.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Sequential changes in DNA methylation patterns of the rat phosphoenolpyruvate carboxykinase gene during development. Benvenisty, N., Mencher, D., Meyuhas, O., Razin, A., Reshef, L. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  9. Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis. Biswas, K.K., Sarker, K.P., Abeyama, K., Kawahara, K., Iino, S., Otsubo, Y., Saigo, K., Izumi, H., Hashiguchi, T., Yamakuchi, M., Yamaji, K., Endo, R., Suzuki, K., Imaizumi, H., Maruyama, I. Hepatology (2003) [Pubmed]
  10. Modulation of cellular proliferation alters glutamine transport and metabolism in human hepatoma cells. Bode, B.P., Souba, W.W. Ann. Surg. (1994) [Pubmed]
  11. Effect of estrogen on the synthesis and secretion of thyroxine-binding globulin by a human hepatoma cell line, Hep G2. Ain, K.B., Refetoff, S., Sarne, D.H., Murata, Y. Mol. Endocrinol. (1988) [Pubmed]
  12. Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity. Hershkoviz, R., Mor, F., Miao, H.Q., Vlodavsky, I., Lider, O. J. Autoimmun. (1995) [Pubmed]
  13. Mutagenic activation of aromatic amines by a human hepatoma cell (Hep G2) supernatant tested by means of Salmonella typhimurium strains with different acetyltransferase activities. Duverger-van Bogaert, M., Dierickx, P.J., Crutzen, M.C. Mutat. Res. (1995) [Pubmed]
  14. Characterization of a novel intracellular heparanase that has a FERM domain. Bame, K.J., Venkatesan, I., Dehdashti, J., McFarlane, J., Burfeind, R. Biochem. J. (2002) [Pubmed]
  15. Amplified ribosomal RNA genes in a rat hepatoma cell line are enriched in 5-methylcytosine. Tantravahi, U., Guntaka, R.V., Erlanger, B.F., Miller, O.J. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  16. Isolation and characterization of a novel promoter for the bovine growth hormone receptor gene. Jiang, H., Okamura, C.S., Lucy, M.C. J. Biol. Chem. (1999) [Pubmed]
  17. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. Spiess, M., Schwartz, A.L., Lodish, H.F. J. Biol. Chem. (1985) [Pubmed]
  18. Chromatin structure and methylation of rat rRNA genes studied by formaldehyde fixation and psoralen cross-linking. Stancheva, I., Lucchini, R., Koller, T., Sogo, J.M. Nucleic Acids Res. (1997) [Pubmed]
  19. Characterization of heparanase from a rat parathyroid cell line. Podyma-Inoue, K.A., Yokote, H., Sakaguchi, K., Ikuta, M., Yanagishita, M. J. Biol. Chem. (2002) [Pubmed]
  20. Mapping heparanase expression in the spinal cord of adult rats. Zhang, Y., Yeung, M.N., Liu, J., Chau, C.H., Chan, Y.S., Shum, D.K. J. Comp. Neurol. (2006) [Pubmed]
  21. Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin. O'Hare, K.B., Hume, I.C., Scarlett, L., Chytrý, V., Kopecková, P., Kopecek, J., Duncan, R. Hepatology (1989) [Pubmed]
  22. Rat carbamyl-phosphate synthetase I gene. Promoter sequence and tissue-specific transcriptional regulation in vitro. Lagacé, M., Howell, B.W., Burak, R., Lusty, C.J., Shore, G.C. J. Biol. Chem. (1987) [Pubmed]
  23. Characterization of the human aldose reductase gene promoter. Wang, K., Bohren, K.M., Gabbay, K.H. J. Biol. Chem. (1993) [Pubmed]
  24. Heparanase expression during normal liver development and following partial hepatectomy. Goldshmidt, O., Yeikilis, R., Mawasi, N., Paizi, M., Gan, N., Ilan, N., Pappo, O., Vlodavsky, I., Spira, G. J. Pathol. (2004) [Pubmed]
  25. Induction of heparanase gene expression in ventricular myocardium of rats with isoproterenol-induced cardiac hypertrophy. Kizaki, K., Okada, M., Ito, R., Yoshioka, K., Hashizume, K., Mutoh, K., Hara, Y. Biol. Pharm. Bull. (2005) [Pubmed]
  26. T lymphocytes affect smooth muscle cell phenotype and proliferation. Rolfe, B.E., Campbell, J.H., Smith, N.J., Cheong, M.W., Campbell, G.R. Arterioscler. Thromb. Vasc. Biol. (1995) [Pubmed]
  27. Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: evidence for cytokine dependence and detection of a novel sulfatase. Bartlett, M.R., Underwood, P.A., Parish, C.R. Immunol. Cell Biol. (1995) [Pubmed]
  28. Analysis of benzo(a)pyrene:DNA adducts formed in cells in culture by immobilized boronate chromatography. Pruess-Schwartz, D., Sebti, S.M., Gilham, P.T., Baird, W.M. Cancer Res. (1984) [Pubmed]
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