Disease relevance of SERPINF2

• We have isolated overlapping phage genomic clones covering an area of 26 kilobases that encodes the human alpha 2-plasmin inhibitor [1].
• alpha 2-Plasmin inhibitor is the most important physiological inhibitor of fibrinolysis; hence, its deficiency results in a severe hemorrhagic diathesis [2].
• Plasma antithrombin III, alpha 2-plasmin inhibitor and plasminogen activities in cases of various liver diseases [3].
• These results suggest that an increased affinity of noncrosslinked fibrin for plasmin(ogen) is contributory to the accelerated fibrinolysis observed in factor XIII deficiency, in addition to an absence of crosslinking of alpha 2-plasmin inhibitor to fibrin [4].
• Fully activable recombinant human plasminogen (rPlg) was expressed in mammalian cells employing either recombinant vaccinia virus or stable lines coexpressing alpha 2-plasmin inhibitor [5].

Psychiatry related information on SERPINF2

• The preliminary results were analyzed in terms of the effects of age, sex, smoking, and alcohol consumption on AAP activity in serum [6].
• Although some of these models have been useful in designing risk reduction programs for API MSM, recent empirical data suggest that the models do not adequately address environmental influences affecting API MSM and limit our choices in prevention strategies to the level of the individual [7].
• At the present time, a small number of programs are attempting to implement various parts of the CWLA and AAP recommendations for health and mental health services for children in out-of-home care [8].
• For those children within the PLI group who function at ceiling on language tests, conversational measures may have the potential to signal change, but this finding has not been subjected to group study or to testing in generalized settings [9].
• AAP releases policy statement on identifying and treating eating disorders [10].

High impact information on SERPINF2

• Molecular basis for congenital deficiency of alpha 2-plasmin inhibitor. A frameshift mutation leading to elongation of the deduced amino acid sequence [11].
• The present study was designed to elucidate the molecular genetic basis of a familial deficiency of alpha 2-plasmin inhibitor (alpha 2PI) [11].
• Conversion by HUVEC was blocked by diisopropyl-fluorophosphate, but not by other serine protease inhibitors, including alpha 2-plasmin inhibitor [12].
• Functional abnormalities were found in: (i) no inhibition of amidolytic activities of plasmin and trypsin, even on prolonged incubation; (ii) no formation of plasmin-antiplasmin complexes in plasma with plasmin added in excess; and (iii) no inhibition of fibrinolysis by fibrin-bound alpha 2-AP [13].
• In the heterozygotes, the presence of abnormal alpha 2-AP did not interfere with several functions of the residual normal alpha 2-AP [13].

Chemical compound and disease context of SERPINF2

• This alpha 2-AP deficiency may well contribute to hemorrhagic diathesis in ANLL independently of the presence or absence of hyperfibrinolysis or DIC [14].
• The levels of plasminogen, alpha 2-plasmin inhibitor and factor XIII decreased and plasma bradykinin increased in toxemia [15].
• We studied the effect of the glucosidase I inhibitor, N-methyl-1-deoxynojirimycin (MdN) and the mannosidase inhibitor, 1-deoxymannojirimycin (dMM) on the biosynthesis and secretion of alpha 2-plasmin inhibitor (alpha 2-PI) and antithrombin III (ATIII) in cultures of human hepatoma (Hep-G2) cells [16].
• Of the 381 isolates from the family Enterobacteriaceae, API and Crystal correctly identified 90.3 and 91.6% by 18 to 24 h without supplemental testing, respectively, and Vitek identified 92.4 and 96.1% following 10 and 18 h of incubation, respectively [17].
• Identification of E. coli O157 was based on indole production, positive latex agglutination for O157 antigen, API 20E test strip results, PCR for the eaeA gene, and the presence of at least one Shiga toxin [18].

Biological context of SERPINF2

• alpha 2-Plasmin inhibitor (alpha 2PI) has been recently characterized as a fast-reacting inhibitor of plasmin in human plasma and appears to play an important role in the regulation of fibrinolysis in vivo [19].
• The alpha 2-plasmin inhibitor gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA [1].
• To elucidate the mechanism by which this mutation leads to the deficiency, a eukaryotic expression plasmid for alpha 2-plasmin inhibitor containing this mutation was constructed and transfected into COS-7 cells for transient expression analysis [2].
• However, when we used a probe for this gene in our efforts to construct a complete physical map of chromosome 18, we discovered that PLI could be excluded from this chromosome [20].
• By using PCR analysis of rodent x human hybrid panels, we have unequivocally assigned the PLI locus to human chromosome 17 [20].

Anatomical context of SERPINF2

• Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase [21].
• These findings suggest that inactivation of alpha 2-plasmin inhibitor and C1 inactivator by leukocyte elastase released in the inflammatory reaction may potentiate pathological proteolysis [21].
• These results suggest that the Glu137 deletion leads to the alpha 2-plasmin inhibitor deficiency by causing a block in its intracellular transport from the endoplasmic reticulum to the Golgi complex [2].
• When blood plasma containing the NH2-terminal 12-residue peptide (N-peptide) of alpha 2-plasmin inhibitor (alpha 2PI; alpha 2-antiplasmin) was clotted in the presence of calcium ions, the N-peptide and alpha 2PI were cross-linked to fibrin by activated coagulation factor XIII [22].
• Urokinase and alpha 2-plasmin inhibitor were also markedly increased in RA synovium [23].

Associations of SERPINF2 with chemical compounds

• The NH2-terminal region, which implements factor XIII-catalyzed cross-linking of alpha 2-plasmin inhibitor to fibrin, is encoded by the 4th exon [1].
• Bleeding episodes due to deficiency of alpha 2-PI in these patients were well controlled by an antifibrinolytic agent, tranexamic acid [24].
• Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method [25].
• Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls [25].
• With both forms of the alpha 2-plasmin inhibitor, a complex stable to acetic acid/urea and gel electrophoresis is present and fully developed 15 s after initiation of the reaction with plasmin [26].

Physical interactions of SERPINF2

• The plasminogen binding as well as the fibrin binding properties of alpha 2-AP were normal [27].
• Unlike 125I-Lys-plasmin, the 48-kDa fragment did not form a complex with alpha 2 plasmin inhibitor [28].
• No evidence of neutrophil migration was observed towards purified complex derived from equine neutrophil elastase and the Spi 1 isoform of equine API, or to crude mixtures of porcine pancreatic elastase and unseparated equine API isoforms, although the same neutrophil preparations actively migrated towards zymosan activated plasma [29].
• These features of alpha 2-PI and its complex with plasmin are similar to those of plasminogen activator inhibitor type 1 (PAI-1) and its complex with plasminogen activators (PAs), thus they may represent some common features of the SERPINS [30].

Regulatory relationships of SERPINF2

• Plasminogen activation by SAK is thus essentially inhibited by alpha 2-PI, but this reaction is not inhibited in fibrin clots [31].
• To elucidate which amino-acid residues played a important role in the inhibitory activity of peptide T-11, we prepared the various synthetic derivatives of peptide T-11 and determined the peptide concentration that inhibited the apparent rate constant of the reaction between plasmin and alpha 2-plasmin inhibitor by 50% (IC50) [32].
• The binding of gp120 to a murine hematopoietic cell line was stimulated by human neutrophil elastase (25-100 nM) and inhibited by IGF I-API [33].
• The ability of Lp(a) to compete with plasmin for fibrin binding displaces plasmin into solution where alpha 2-AP rapidly inhibits this proteinase [34].
• During blood coagulation alpha 2-plasmin inhibitor (alpha 2PI) is cross-linked with fibrin by an activated fibrin-stabilizing factor (FSFa) plasma transglutaminase, activated coagulation factor XIII) [35].

Other interactions of SERPINF2

• This study has examined the interaction between human leukocyte elastase and alpha 2-plasmin inhibitor, or C1 inactivator, inhibitors of proteases of the complement, kinin, coagulation, and fibrinolytic enzyme systems [21].
• Similarly, in a purified system composed of plasminogen, fibrinogen and alpha 2-plasmin inhibitor (alpha 2-PI, alpha 2-antiplasmin), such a fibrin clot increased the activity of SAK significantly [31].
• PLG was significantly decreased 4 and 8 weeks after rhEPO treatment, and ATIII and alpha 2 PI were significantly decreased 8 weeks after rhEPO treatment. alpha 2 PIC was significantly increased 8 weeks after rhEPO treatment, and XL-FDP was significantly increased 4 and 8 weeks after rhEPO treatment [36].
• The data suggest that alpha 2-PI may originally have inhibited some protease other than plasmin, and protein C may have had an inhibitor different from the present one early in its evolutionary history [37].
• However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates [37].

Analytical, diagnostic and therapeutic context of SERPINF2

• Immunoprecipitation analysis and enzyme-linked immunosorbent assay revealed that the mutant alpha 2-plasmin inhibitor synthesized is mostly retained within the cells as an endoglycosidase H-sensitive form, and only a small portion of it is secreted into the medium as a neuraminidase-sensitive form [2].
• The human gene for the alpha 2-plasmin inhibitor (PLI) had been assigned by others to the pericentromeric region of chromosome 18 by in situ hybridization [20].
• Interaction of urokinase (UK) activated plasmin with tranexamic acid and alpha 2 plasmin inhibitor (alpha 2PI) was studied by using a chromogenic substrate (S-2251) and immunoelectrophoresis [38].
• Fibrinogen, euglobulin lysis time (ELT), tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor activity (PA-inhibitor) and alpha 2-antiplasmin (alpha 2-AP) were measured pre- and postoperatively in 60 patients undergoing total hip replacement [39].
• The alpha 2-plasmin inhibitor and plasminogen activator inhibitor-1 levels were significantly (p < 0.05) greater in the minimal-dose and low-dose groups than in the control group after bypass, suggesting the prevention of fibrinolysis by both aprotinin doses [40].

References