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

• A synthetic serine protease inhibitor, nafamostat mesilate (NM), which is commonly used for the treatment of pancreatitis and disseminated intravascular coagulation in Japan, also inhibited the secretion of prostasin in M-1 cells [11].
• Urinary trypsin inhibitor (UTI), a serine protease inhibitor, is cytoprotective against ischemia-reperfusion injury in the liver, intestine, kidney, heart, and lung through its antiinflammatory activity [12].
• Male Sprague-Dawley rats were administrated the serine protease inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, Nafamostat) either intraluminally into the gut or intravenously after a laparotomy (trauma) and then subjected to 90 min of hemorrhagic shock (T/HS) or sham shock (T/SS) [13].
• Recently, it was reported that a low dose of nafamostat mesilate (NM), a serine protease inhibitor that is widely used to treat disseminated intravascular coagulation (DIC) and acute pancreatitis, can selectively inhibit human tryptase activity [14].
• The aim of this study was to determine the effects of a synthetic serine protease inhibitor, gabexate mesilate (GM), in rats with ischemia-reperfusion (I-R) damage due to unilateral testicular torsion [15].

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

• 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 [17].

Other interactions of LOC299282

• They were synthesized as precursors of comparable sizes (45 kDa), which were post-translationally modified by N-glycosylation at three (SPI-3) or four (SPI-1 and SPI-2) sites [24].
• Growth hormone-mediated transcriptional activation of the rat serine protease inhibitor 2.1 gene involves both interleukin-1 beta-sensitive and -insensitive pathways [28].
• IGF-I and serine protease inhibitor 2.1 nuclear transcript abundance in rat liver during protein restriction [29].
• Electromobility shift assays using hepatic nuclear extracts from these neonates and the GH response element from the serine protease inhibitor 2.1 promoter showed signal transducer and activator of transcription 5 (Stat5) binding in response to GH in extracts from d-7 rats only [30].
• In contrast, the ability to stimulate transcription of the serine protease inhibitor 2.1 promoter by the GHR was not affected by the phenylalanine 346 to alanine mutation [31].

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].

References