Disease relevance of Serpina5

• The results suggested that PCI efficiently inhibits not only the anticoagulant and anti-inflammatory activities of exogenously injected human activated protein C (APC) but also that of endogenously produced APC in mice with endotoxemia [1].
• Hybrids between mouse PCC4-azal teratocarcinoma cells and rat epithelial intestinal villus cells (PCI hybrids) are phenotypically teratocarcinoma cells [2].
• The serine protease inhibitors alpha1-antitrypsin, eglin C, and aprotinin protected against toxicity [3].
• In contrast, PCI had no effect on 3.5% FeCl(3)-induced carotid artery thrombosis in mice [4].
• When absorbed with adenocarcinoma anti-serum, cells cultivated under standard cell culture conditions, or cultured in presence of antitrypsin became less transplantable, whereas, cells grown in cotton-stoppered glass bottles or in presence of the extracellular protease maintained their transplantability [5].

High impact information on Serpina5

• Using recombinant inbred mouse strains, a tentative linkage map of chromosome 12 has been worked out that incorporates these markers, the c-fos oncogene, Igh, and Pre-1/alpha 1 antitrypsin [6].
• Adoptive transfer experiments demonstrated that AAT gene therapy attenuated cellular immunity associated with beta cell destruction [7].
• T cell receptor spectratyping indicated that AAT gene therapy altered T cell repertoire diversity in splenocytes from NOD mice [7].
• In addition, PCI, PC, and uPAR had a germinal origin [8].
• Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development [8].

Biological context of Serpina5

• This study demonstrates that AAT gene therapy attenuates cell-mediated autoimmunity, alters the T cell receptor repertoire, and efficiently prevents type 1 diabetes in the NOD mouse model [7].
• Molecular cloning and tissue distribution of mouse protein C inhibitor (PCI) [9].
• Background: Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems [10].
• The eight subunits of the CSN possess sequence homologies with the polypeptides of the 26S proteasome lid complex and just like the lid, the CSN consists of six subunits with PCI (proteasome, COP9 signalosome, initiation factor 3) domains and two components with MPN (Mpr-Pad1-N-terminal) domains [11].

Anatomical context of Serpina5

• Collectively, these results support the hypothesis that PCI may contribute to proteolysis equilibrium within the testis by acting in tandem with urokinase in Leydig cells and with PC and/or urokinase in spermatogenic cells [8].
• PCI transcripts accumulated rapidly in the male gonad, from 12.5 d postcoitum onward [8].
• Northern blot and immunohistochemical analyses demonstrated that human PCI is expressed in liver hepatocytes, renal epithelial cells as well as heart, brain and reproductive organs of the TG mice [1].
• In humans, protein C inhibitor (PCI) is expressed in various tissues and present in many body fluids including plasma and seminal fluid [1].
• Osteoblast and bone final concentrates comigrated with Trasylol but were electrophoretically distinct from alpha 1-antiproteinase [12].

Associations of Serpina5 with chemical compounds

• Next, we evaluated the effect of PCI on coagulation, inflammation and tissue damage in lipopolysaccharide-treated TG mice [1].
• This fatty acid modification potentiated the inhibitory activity of the original PCI peptides and both myr-PCI(Y) and myr-PCI(F) suppressed the PIP2-hydrolyzing activity of purified PLC isoforms in vitro [13].
• Cadmium-induced pulmonary injury in mouse: a relationship with serum antitrypsin activity [14].

Other interactions of Serpina5

• In adult testes, PCI and uPAR immunoreactivities were also present in Leydig cells [8].

Analytical, diagnostic and therapeutic context of Serpina5

• These results strongly suggest that rAAV1-mediated AAT gene therapy may be useful as a novel approach to prevent type 1 diabetes [7].
• Western blot and immunohistochemistry analyses confirmed that male, but not female, fetal gonads produced PCI, and that Leydig cells are the site of PCI synthesis [8].
• Molecular cloning and sequence analysis of the mouse protein C inhibitor gene [15].
• Bronchoalveolar lavage fluid (BALF) levels of thrombin-antithrombin complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-alpha were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice [10].

References