Disease relevance of SERPINA5

• Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma [1].
• Protein C inhibitor (plasminogen activator inhibitor-3) expression in the CWR22 prostate cancer xenograft [2].
• A human genomic phage DNA library was screened using the 32P-labeled protein C inhibitor cDNA as a probe and a phage genomic clone that contained the full length of the inhibitor gene, including the 5'- and 3'-flanking region, was isolated [3].
• Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line [4].
• A cDNA library in lambda-phage lambda gt11 containing DNA inserts prepared from human liver mRNA was screened with monoclonal antibodies to human protein C inhibitor [5].

Psychiatry related information on SERPINA5

• Depressive syndromes and, particularly schizophrenic and paranoid psychoses were more frequent among the PCI than among the PCO subjects [6].
• Adequate time for thoughtful decision-making, scheduling complexity, informed consent, and physician reimbursement favor PCI on a subsequent day [7].
• However, treatment of acute myocardial infarction and secondary prevention considerably have been improved within the past years including early revascularization by PCI, the routine use of beta-blockers, statins and ACE-inhibitors as well as cardiac rehabilitation for improving life style measures [8].
• Pain-coping strategies in chronic pain patients: psychometric characteristics of the pain-coping inventory (PCI) [9].
• When trials with a symptom duration < 6 hours (median 130 min) were considered, PCI-related delay still correlated with an absolute risk reduction in 30-day mortality with a time to equipoise of 57 min (p = 0.03) [10].

High impact information on SERPINA5

• Protein C inhibitor (PCI) is a nonspecific, heparin-binding serpin (serine protease inhibitor) that inactivates many plasmatic and extravascular serine proteases by forming stable 1:1 complexes [11].
• Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility [11].
• Here we show that PCI(-/-) mice are apparently healthy but that males of this genotype are infertile [11].
• Conditioned medium from the rhesus monkey kidney cell line CCL7.1 was analyzed on immunoblots, showing a 57,000-D protein band that comigrated with human plasma PCI [12].
• PCI is found in urine and binds to kidney epithelial cells [12].

Chemical compound and disease context of SERPINA5

• Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment [13].
• The N-glycosylation site mutants of human protein C inhibitor (PCI; N230S, N243Q, N319Q, N230S/N243Q, and N230S/N319Q) were prepared by amino acid replacement of the asparagine residue with a serine or glutamine residue using site-directed mutagenesis and expressed in the baculovirus/insect cell expression system [14].
• METHODS AND RESULTS: From June 2001 to November 2002, 507 patients with acute myocardial infarction, who were transferred to a PCI centre, were randomised to early, pre-hospital initiation of Tirofiban (Early) or to initiation in the catheterisation laboratory (Late) [15].
• Effect of urinary protein C inhibitor on lipopolysaccharide-induced disseminated intravascular coagulation in rats [16].
• We sought to investigate the effect of L-arginine administration on the extent of lymphocyte activation and anti-oxLDL antibodies in patients with unstable angina undergoing PCI with stent placement [17].

Biological context of SERPINA5

• Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1 [18].
• Thrombomodulin enhances the reactivity of thrombin with protein C inhibitor by providing both a binding site for the serpin and allosterically modulating the activity of thrombin [19].
• No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line [1].
• The deduced amino acid sequence of rat PCI showed an 85.7% and 62.2% homology with that of mouse and human PCIs, respectively [20].
• These findings suggest that the PCI gene expression in rat seminal vesicles is under androgen control [20].

Anatomical context of SERPINA5

• Most of the hK2 in seminal plasma forms an inactive complex with protein C inhibitor (PCI), a serpin secreted by seminal vesicles [21].
• Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis [1].
• The main sources of seminal PCI are the seminal vesicles, where it remains fully active [22].
• Protein C inhibitor (PCI), a serine-proteinase inhibitor first purified from human blood plasma, occurs at high concentrations (3-4 microM) in seminal fluid in both a high-molecular-mass and low-molecular-mass form [23].
• Purified functionally active human blood plasma-derived as well as inactive semen-derived PCI inhibited both binding and penetration of zona-free hamster oocytes by human sperm [22].

Associations of SERPINA5 with chemical compounds

• Using this assay, time, dose, and heparin-dependent complexes were detected when uPA was incubated with normal plasma or purified urinary PCI, whereas no complexes were measurable using PCI-immunodepleted plasma [24].
• cis-elements required for expression of human protein C inhibitor gene in HepG2 cells and its androgen-dependent expression in rat reproductive organs [20].
• The PCI mRNA expression in seminal vesicles was significantly decreased after castration or after 17beta-estradiol treatment [20].
• Sg II bound to the solid-phase complex of diisopropylfluorophosphate (iPr2FP) and PSA with an apparent dissociation constant (kd) of 41 nM and to PCI with a Kd of 28 nM [25].
• The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment [4].
• A peptide corresponding to the heparin-binding site of PCI abolished the stimulatory effect of PS on aPC inhibition [26].
• The second-order rate constants (m(-1) min(-1)) of the reaction between HGFA and PCI in the presence or absence of heparin (10 U mL(-1)) were 4.3 x 10(6) and 4.0 x 10(6), respectively [27].
• Exosite-2 residues (Arg89, Arg93, Glu94, Arg98, Arg245, Arg248, and Gln251) were critical for heparin-accelerated inhibition of thrombin by PCI [28].

Physical interactions of SERPINA5

• In these plasma samples uPA-PCI complexes were present in a concentration corresponding to 21% to 25% of inactive uPA antigen [24].
• Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited by PCI [29].
• Seminal plasma collected in the absence of extrinsic inhibitors contained 1.8 +/- 0.6 nM tKK:PCI complex and 4.7 +/- 2.8 nM immunoreactive tKK (mean +/- SD, n = 10), which indicates that about 28% of the total tKK immunoreactivity is forming complexes with PCI [30].
• A few per cent of PSA in semen is complexed to the protein C inhibitor [31].
• A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes [32].

Enzymatic interactions of SERPINA5

• PCI was found to inhibit the PSA-catalyzed degradation of insoluble coagula Sg I + II by forming a PSA-PCI complex [25].
• The residues Phe353-Arg354-Ser355 (P2-P1-P1') constitute part of the reactive site loop of PCI with the Arg-Ser peptide bond being cleaved by the proteinase [33].

Regulatory relationships of SERPINA5

• We conclude that TM enhances the reactivity of PCI with thrombin by providing both a binding site for the serpin and a conformational modulation of the extended binding pocket of thrombin [19].
• This suggests that PCI can up regulate TAFI activation by inhibiting the protein C activation [34].
• In blood plasma, PCI is present at ~0.08 muM and inactivates activated protein C and other coagulation and fibrinolytic enzymes [22].
• These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells [1].
• Purified human PCI inhibited the amidolytic activity of purified boar acrosin with an apparent second-order rate constant of 3.7 x 10(4) M-1.s-1 [35].

Other interactions of SERPINA5

• The role of PCI for urokinase (uPA) inhibition in vivo was investigated [24].
• Further studies revealed that the substitution of Arg35 of thrombin with an Ala also resulted in an order of magnitude enhancement in reactivity of the protease with both PCI and AT-PCIH-helix independent of TM [19].
• Substrates derived from PCI were the most sensitive for both hK1 and hK2 with specificity constants of about 10(7) M-1. s-1 [21].
• However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates [36].
• Addition of PCI to normal plasma and protein C-deficient plasma resulted in a minor prolongation of the clotting time [29].

Analytical, diagnostic and therapeutic context of SERPINA5

• In freshly collected ejaculates, the rate of PCI-PSA complex formation measured by IFMA was similar to that observed between the purified proteins, and paralleled the appearance of SDS-stable complexes by immunoblotting [23].
• Glandular kallikrein and protein-C inhibitor (PCI)-hK2 complex, a serpin protease inhibitor that binds hK2, were purified to homogeneity by affinity and size-exclusion chromatography [37].
• PCI antigen was assayed by ELISA and PCI activity was measured by its capability to form complexes with APC in the presence of heparin [38].
• By Northern blot, immunohistochemistry, and in situ hybridization, we found that PCI was expressed in both benign and malignant prostate tissues [2].
• Conclusive evidence of a local synthesis of PCI in the four male sex glands was provided by Northern blot analysis of RNA from these organs [39].

References