The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Gene Review

LOC299282  -  Serine protease inhibitor

Rattus norvegicus

Synonyms: Ab1-021, CPI-23, CPi-23, Contrapsin-like protease inhibitor 3, SPI-1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of LOC299282

  • We found that a high level of spi 2.1 gene transcription correlates with hypersensitivity of the promoter to deoxyribonuclease I (DNase I) and maximal occupancy of the GAGA box (GHRE-I) [1].
  • Induction of SPI-3 mRNA, encoding a serine protease inhibitor, in gerbil hippocampus after transient forebrain ischemia [2].
  • Chymostatin, a serine protease inhibitor that does not prevent the activation of NF-kappaB, had no effect on the organ injury/failure caused by hemorrhagic shock [3].
  • Coinfusion of Abeta40 with the serine protease inhibitor aprotinin also increased diffuse extracellular deposition but reduced astrocytosis and TUNEL and was not associated with intracellular Abeta staining [4].
  • Ecotin, a serine protease inhibitor found in the periplasm of Escherichia coli, is unique in its ability and mechanism of inhibiting serine proteases of a broad range of substrate specificity [5].

High impact information on LOC299282

  • As C1 esterase inhibitor (C1-INH) is a serine protease inhibitor involved in such processes, the aim of this work was to study C1-INH synthesis in KC and, by comparison, in peritoneal macrophages (PM) and blood monocytes (MC) of the rat [6].
  • This conversion was also inhibited by pretreatment with the serine protease inhibitor benzamidine (10 mM) but not the cysteine protease inhibitor E64 (100 microM) [7].
  • We explored this idea using camostat mesilate, a serine protease inhibitor, to determine its effects and mechanisms of action in vivo [8].
  • SP, aprotinin (serine protease inhibitor), and ketotifen (mast cell stabilizer) were infused into the splenic artery of rats [9].
  • Pretreatment with the nonspecific serine protease inhibitor, soybean trypsin inhibitor (15 mg/kg), significantly attenuated the clearance responses normally observed during luminal perfusion with FMLP [10].

Chemical compound and disease context of LOC299282


Biological context of LOC299282

  • Analysis of proteins binding to the proximal promoter region of two rat serine protease inhibitor genes [16].
  • The 42 bp sequence which is found only within the SPI 2.3 promoter interacts with two ubiquitous factors, one of which is related to NF kappa B. Acute inflammation does not significantly affect the protein binding patterns observed with the SPI 2.1 or 2.3 proximal promoter sequences [16].
  • Thus, a GH-activated signaling pathway stimulates Spi 2.1 gene expression through a unique mechanism that does not appear to involve known members of the STAT family of transcription factors [17].
  • Members of the serpin (serine protease inhibitor) superfamily of genes are well represented in both human and murine genomes [18].
  • DNase I footprinting using purified GHINF yields a protected region of -149/-115 on the rat serine protease inhibitor 2.1 (Spi 2.1) promoter encompassed within the growth hormone response element (GHRE) [19].

Anatomical context of LOC299282

  • TNF-alpha, IL-1beta, and IL-6 also inhibit GH-induced Spi 2.1 mRNA expression in hepatocytes [20].
  • Regulation of two rat serine-protease inhibitor gene promoters by somatotropin and glucocorticoids. Study with intact hepatocytes and cell-free systems [21].
  • However, none of the most largely liver expressed C/EBP species (i.e. alpha, beta and delta) activated the spi 2.3 3' UTR silencer function in NIH 3T3 cells, suggesting that binding of those transcription factors did not mediate the transcriptional repression [22].
  • The current studies found that serine protease inhibitor aprotinin blocked the secretion of prostasin in a mouse cortical collecting duct (CCD) cell line (M-1 cells) [11].
  • We examined the effect of the synthetic serine protease inhibitor FUT-175 (developed as a potent inhibitor of thrombin and the complement system) on vascular lesions using balloon dilatation-induced neointimal formation in the carotid artery of rats [23].

Associations of LOC299282 with chemical compounds

  • Rat hepatocytes have the potential to secrete three similar acidic glycoproteins, serine protease inhibitors 1, 2 and 3 (SPI-1, SPI-2, SPI-3), recognized by the same antibodies [24].
  • cis-Acting elements controlling transcription from rat serine protease inhibitor 2.1 gene promoter. Characterization of two growth hormone response sites and a dominant purine-rich element [25].
  • Normal rat hepatocytes were transiently transfected with constructs harboring deleted or mutated versions of the spi 2.1 proximal promoter region fused to the chloramphenicol acetyltransferase gene [25].
  • GH treatment induced tyrosine phosphorylation of several hepatic nuclear proteins, activated Stats1, 3, and 5, stimulated Spi 2.1 gene expression, and inhibited albumin gene transcription [26].
  • To block intrapancreatic trypsinogen activation, a potent and cell-permeable serine-protease inhibitor, Pefabloc, was used [27].

Regulatory relationships of LOC299282


Other interactions of LOC299282


Analytical, diagnostic and therapeutic context of LOC299282

  • The three serine protease inhibitor (SPI) rat genes expressed preferentially in liver share considerable structural features and, nonetheless, are transcriptionally regulated in completely different manners, more particularly after hypophysectomy or upon acute inflammation [16].
  • To define the mechanism of this process, hepatic nuclear extracts were analyzed by electrophoretic mobility shift assays using a DNA fragment (-147 to -103) of the Spi 2.1 gene [32].
  • Prolongation of allograft survival in rat heterotopic heart transplantation by TLCK, a serine protease inhibitor [33].
  • OBJECTIVE: The non-specific serine protease inhibitor aprotinin is currently used to reduce blood loss and the need for blood transfusion after cardiopulmonary bypass [34].
  • These results demonstrate the clinical potential for this novel serine protease inhibitor to prevent GVD in solid organ transplantation [35].


  1. Transcription of the rat serine protease inhibitor 2.1 gene in vivo: correlation with GAGA box promoter occupancy and mechanism of cytokine-mediated down-regulation. Simar-Blanchet, A.E., Legraverend, C., Thissen, J.P., Le Cam, A. Mol. Endocrinol. (1998) [Pubmed]
  2. Induction of SPI-3 mRNA, encoding a serine protease inhibitor, in gerbil hippocampus after transient forebrain ischemia. Tsuda, M., Kitagawa, K., Imaizumi, K., Wanaka, A., Tohyama, M., Takagi, T. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  3. Calpain inhibitor I reduces the activation of nuclear factor-kappaB and organ injury/dysfunction in hemorrhagic shock. McDonald, M.C., Mota-Filipe, H., Paul, A., Cuzzocrea, S., Abdelrahman, M., Harwood, S., Plevin, R., Chatterjee, P.K., Yaqoob, M.M., Thiemermann, C. FASEB J. (2001) [Pubmed]
  4. Protease inhibitor coinfusion with amyloid beta-protein results in enhanced deposition and toxicity in rat brain. Frautschy, S.A., Horn, D.L., Sigel, J.J., Harris-White, M.E., Mendoza, J.J., Yang, F., Saido, T.C., Cole, G.M. J. Neurosci. (1998) [Pubmed]
  5. Isolation of a high affinity inhibitor of urokinase-type plasminogen activator by phage display of ecotin. Wang, C.I., Yang, Q., Craik, C.S. J. Biol. Chem. (1995) [Pubmed]
  6. C1 esterase inhibitor gene expression in rat Kupffer cells, peritoneal macrophages and blood monocytes: modulation by interferon gamma. Armbrust, T., Schwögler, S., Zöhrens, G., Ramadori, G. J. Exp. Med. (1993) [Pubmed]
  7. Intracellular activation of digestive zymogens in rat pancreatic acini. Stimulation by high doses of cholecystokinin. Leach, S.D., Modlin, I.M., Scheele, G.A., Gorelick, F.S. J. Clin. Invest. (1991) [Pubmed]
  8. Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-beta. Okuno, M., Akita, K., Moriwaki, H., Kawada, N., Ikeda, K., Kaneda, K., Suzuki, Y., Kojima, S. Gastroenterology (2001) [Pubmed]
  9. Substance P attenuates gastric mucosal hyperemia after stimulation of sensory neurons in the rat stomach. Grönbech, J.E., Lacy, E.R. Gastroenterology (1994) [Pubmed]
  10. Neutrophilic proteases: mediators of formyl-methionyl-leucyl-phenylalanine-induced ileitis in rats. von Ritter, C., Be, R., Granger, D.N. Gastroenterology (1989) [Pubmed]
  11. Inhibition of prostasin secretion by serine protease inhibitors in the kidney. Iwashita, K., Kitamura, K., Narikiyo, T., Adachi, M., Shiraishi, N., Miyoshi, T., Nagano, J., Tuyen, d.o. .G., Nonoguchi, H., Tomita, K. J. Am. Soc. Nephrol. (2003) [Pubmed]
  12. Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats. Yano, T., Anraku, S., Nakayama, R., Ushijima, K. Anesthesiology (2003) [Pubmed]
  13. Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury. Deitch, E.A., Shi, H.P., Lu, Q., Feketeova, E., Xu, d.a. .Z. Shock (2003) [Pubmed]
  14. Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis. Isozaki, Y., Yoshida, N., Kuroda, M., Handa, O., Takagi, T., Kokura, S., Ichikawa, H., Naito, Y., Okanoue, T., Yoshikawa, T. Scand. J. Gastroenterol. (2006) [Pubmed]
  15. Effects of gabexate mesilate on ischemia-reperfusion-induced testicular injury in rats. Gezici, A., Ozturk, H., Buyukbayram, H., Ozturk, H., Okur, H. Pediatr. Surg. Int. (2006) [Pubmed]
  16. Analysis of proteins binding to the proximal promoter region of two rat serine protease inhibitor genes. Rossi, V., Rouayrenc, J.F., Paquereau, L., Vilarem, M.J., Le Cam, A. Nucleic Acids Res. (1992) [Pubmed]
  17. Growth hormone rapidly activates rat serine protease inhibitor 2.1 gene transcription and induces a DNA-binding activity distinct from those of Stat1, -3, and -4. Thomas, M.J., Gronowski, A.M., Berry, S.A., Bergad, P.L., Rotwein, P. Mol. Cell. Biol. (1995) [Pubmed]
  18. Expression patterns of murine antichymotrypsin-like genes reflect evolutionary divergence at the Serpina3 locus. Horvath, A.J., Forsyth, S.L., Coughlin, P.B. J. Mol. Evol. (2004) [Pubmed]
  19. Growth hormone induction of hepatic serine protease inhibitor 2.1 transcription is mediated by a Stat5-related factor binding synergistically to two gamma-activated sites. Bergad, P.L., Shih, H.M., Towle, H.C., Schwarzenberg, S.J., Berry, S.A. J. Biol. Chem. (1995) [Pubmed]
  20. Inhibition of growth hormone action in models of inflammation. Bergad, P.L., Schwarzenberg, S.J., Humbert, J.T., Morrison, M., Amarasinghe, S., Towle, H.C., Berry, S.A. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  21. Regulation of two rat serine-protease inhibitor gene promoters by somatotropin and glucocorticoids. Study with intact hepatocytes and cell-free systems. Paquereau, L., Vilarem, M.J., Rossi, V., Rouayrenc, J.F., Le Cam, A. Eur. J. Biochem. (1992) [Pubmed]
  22. Characterization of three transcriptional repressor sites within the 3' untranslated region of the rat serine protease inhibitor 2.3 gene. Paul, C., Simar-Blanchet, A.E., Ro, H.S., Le Cam, A. Eur. J. Biochem. (1998) [Pubmed]
  23. Prevention of neointimal formation by a serine protease inhibitor, FUT-175, after carotid balloon injury in rats. Sawada, M., Yanamoto, H., Nagata, I., Hashimoto, N., Nakahara, I., Akiyama, Y., Kikuchi, H., Macdonald, R.L. Stroke (1999) [Pubmed]
  24. Molecular characterization of three rat liver serine-protease inhibitors affected by inflammation and hypophysectomy. Protein and mRNA analysis and cDNA cloning. Pages, G., Rouayrenc, J.F., Le Cam, G., Mariller, M., Le Cam, A. Eur. J. Biochem. (1990) [Pubmed]
  25. cis-Acting elements controlling transcription from rat serine protease inhibitor 2.1 gene promoter. Characterization of two growth hormone response sites and a dominant purine-rich element. Le Cam, A., Pantescu, V., Paquereau, L., Legraverend, C., Fauconnier, G., Asins, G. J. Biol. Chem. (1994) [Pubmed]
  26. Contrasting acute in vivo nuclear actions of growth hormone and prolactin. Le Stunff, C., Gronowski, A.M., Rotwein, P. Mol. Cell. Endocrinol. (1996) [Pubmed]
  27. Induction of IkappaB-kinase by cholecystokinin is mediated by trypsinogen activation in rat pancreatic lobules. Tando, Y., Algül, H., Schneider, G., Weber, C.K., Weidenbach, H., Adler, G., Schmid, R.M. Digestion (2002) [Pubmed]
  28. Growth hormone-mediated transcriptional activation of the rat serine protease inhibitor 2.1 gene involves both interleukin-1 beta-sensitive and -insensitive pathways. Le Cam, A., Paul, C., Thissen, J.P. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  29. IGF-I and serine protease inhibitor 2.1 nuclear transcript abundance in rat liver during protein restriction. Hayden, J.M., Straus, D.S. J. Endocrinol. (1995) [Pubmed]
  30. Growth hormone action in hypothyroid infant rats. Humbert, J.T., Bergad, P.L., Masha, O., Stolz, A.M., Kaul, S., Berry, S.A. Pediatr. Res. (2000) [Pubmed]
  31. Identification of phenylalanine 346 in the rat growth hormone receptor as being critical for ligand-mediated internalization and down-regulation. Allevato, G., Billestrup, N., Goujon, L., Galsgaard, E.D., Norstedt, G., Postel-Vinay, M.C., Kelly, P.A., Nielsen, J.H. J. Biol. Chem. (1995) [Pubmed]
  32. Binding of a growth hormone-inducible nuclear factor is mediated by tyrosine phosphorylation. Berry, S.A., Bergad, P.L., Whaley, C.D., Towle, H.C. Mol. Endocrinol. (1994) [Pubmed]
  33. Prolongation of allograft survival in rat heterotopic heart transplantation by TLCK, a serine protease inhibitor. Morrissey, P.E., Gollin, G., Brusett, K., Marks, W.H. Transplantation (1994) [Pubmed]
  34. Aprotinin impairs coronary endothelial function and down-regulates endothelial NOS in rat coronary microvascular endothelial cells. Ulker, S., McKeown, P.P., Bayraktutan, U. Cardiovasc. Res. (2002) [Pubmed]
  35. Viral serine proteinase inhibitor (SERP-1) effectively decreases the incidence of graft vasculopathy in heterotopic heart allografts. Hausen, B., Boeke, K., Berry, G.J., Morris, R.E. Transplantation (2001) [Pubmed]
WikiGenes - Universities