Disease relevance of Serpina3k

• Glia-derived nexin (GDN), also known as protease nexin I, is a serine protease inhibitor of deduced relative molecular mass 41,700, identified in conditioned media of glioma cells by its neurite-promoting activity [1].
• Intravitreal injection of KBP inhibited retinal neovascularization in an OIR model [2].
• Expression and characterization of rat kallikrein-binding protein in Escherichia coli [3].
• 5' RACE analysis of rat kidney and hepatoma RNAs showed the presence of a 5' extended mRNA with a sequence complementary to the Spi2 mRNA [4].
• The administration of a high-dose of a serine protease inhibitor is recommended in patients complicated by multiple organ failure (MOF), including adult respiratory distress syndrome (ARDS), induced by acute pancreatitis [5].

High impact information on Serpina3k

• Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning [6].
• GHR-P63 mRNA, virtually undetectable in hepatocytes from hypophysectomized rats, could be hormonally re-induced to subnormal levels both in vivo by treating animals with hormones and in vitro by incubating the defective cells with hormones [7].
• Strong sequence homologies, both at the nucleotide and the amino acid levels were found between GHR-P63 and several serum protease inhibitors, more particularly mouse contrapsin and human alpha 1-antichymotrypsin [7].
• In this study, we have shown that concentrations of the broad-spectrum serine protease inhibitor diisopropylfluorophosphate that did not inhibit tumor cell DNA and protein synthesis completely abrogated tumor-induced red blood cell cytolysis [8].
• Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system. Evidence for a role in neurite outgrowth [9].

Chemical compound and disease context of Serpina3k

• Camostat mesilate (FOY305), a synthetic serine protease inhibitor and has been developed as a drug for pancreatitis, is effective in suppressing acute experimental allergic encephalomyelitis in Lewis rats [10].
• 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 [11].

Biological context of Serpina3k

• 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 [12].
• A full length cDNA clone encoding the kallikrein-binding protein was isolated from a rat liver cDNA library by immunoscreening and the translated amino acid sequence matches the amino-terminal 29-amino acid sequence of the binding protein [13].
• 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) [14].
• GH stimulated STAT5 and ERK1/2 phosphorylation, IGF-I, and Spi 2.1 mRNA expression [15].
• To obtain further information on the molecular structure, a cDNA clone (lambda CPi-21) for this contrapsin-like protease inhibitor was isolated from a rat liver cDNA library [16].

Anatomical context of Serpina3k

• Dot blot analysis shows that kallikrein-binding protein is expressed at high levels in the liver and at low levels in the lung, salivary gland, and kidney [13].
• A low molecular weight serine protease inhibitor, named trypstatin, was purified from rat peritoneal mast cells [17].
• KBP competed with (125)I-VEGF for binding to endothelial cells and down-regulated VEGF production in endothelial cells and in the retina of the OIR rat model [2].
• Moreover, KBP decreased vascular leakage in the retina, iris and choroid in rats with OIR [2].
• These findings suggest that a cell-intrinsic, thyroid-hormone-regulated timer determines when the first oligodendrocytes develop [18].

Associations of Serpina3k with chemical compounds

• GHR-P63 ('growth hormone-regulated protein of 63,000 daltons') is an acidic glycoprotein secreted by rat hepatocytes whose synthesis is abolished upon hypophysectomy [7].
• Conversely, negative acute-phase reactants are reduced on inflammation: alpha1-inhibitor III, alpha2-HS-glycoprotein, kallikrein-binding protein and transthyretin (all reduced to between 1/2 to 1/3 of the baseline levels), retinol-binding protein (to about 1/2 to 1/4) and albumin (to 2/3) [19].
• Three highly homologous serine protease inhibitors, SPI-1, SPI-2 and SPI-3 (contrapsins), are synthesized in rat liver [20].
• The 1.6-kb cDNA insert contained an open reading frame that encodes a 416-residue polypeptide (CPi-21), in which the first 29 residues were suggested to comprise a signal peptide by comparison with the NH2-terminal sequence of the purified protein [16].
• Phenylmethylsulfonyl fluoride, a serine protease inhibitor, inhibited both free tonin and the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex [21].

Other interactions of Serpina3k

• SPI-1 and SPI-2 mRNAs were of similar sizes (1.8 kb), and were smaller than that of SPI-3 (2.2 kb); the difference corresponded to a longer, 3'-end untranslated sequence [22].
• The effect of aprotinin (a serine protease inhibitor) on renal function and renin release [23].
• Inhibition of rat tissue kallikrein gene family members by rat kallikrein-binding protein and alpha 1-proteinase inhibitor [24].
• Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively [25].
• We show the appearance of a 'cross-reacting material' for induced tyrosine aminotransferase of old rats compared to basal enzyme; this cross-reacting material can be provoked in adult rats after injection of cycloheximide, and suppressed in adult and old rats after injection of a serine protease inhibitor (tosylphenylalanine chloromethylketone) [26].

Analytical, diagnostic and therapeutic context of Serpina3k

• In agreement with sequence data, GHR-P63 purified from rat blood by affinity chromatography was found to carry an anti-trypsin activity [7].
• Molecular cloning and analysis of the rat kallikrein-binding protein gene [27].
• Kallikrein-binding protein was purified to apparent homogeneity from rat serum by Affi-Gel Blue, DEAE-Sepharose CL-6B, Sephacryl S-200 chromatography, and preparative gel electrophoresis or high performance liquid chromatography [13].
• Western blot and radioimmunoassay showed a distribution of the kallikrein-binding protein in serum, urine, and various tissues with a 5-10-fold lower amount in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY) [13].
• The decreased KBP levels were confirmed by Western blot analysis [28].

References