Disease relevance of Cpb2

• An increase in CPR activity may facilitate rapid inactivation of inflammatory mediators generated at the site of Gram-negative bacterial infection and may consequently prevent septic shock [1].
• Tumor growth and metastasis are not affected in thrombin-activatable fibrinolysis inhibitor-deficient mice [2].
• TAFI deficiency did not improve survival rate compared with the wild-type in thrombin-induced thromboembolism, factor X coagulant protein-induced thrombosis, and endotoxin-induced disseminated intravascular coagulation [3].
• These results suggest that the anti-fibrinolytic activity of TAFI promotes lung fibrosis by hindering the rate at which fibrin is degraded [4].
• BACKGROUND/OBJECTIVE: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma carboxypeptidase that renders a fibrin-containing thrombus less sensitive to lysis [5].
• The results of this study suggest that increased renal activity of plasmin in TAFI-deficient mice causes increased renal interstitial fibrosis in obstructive nephropathy [6].

High impact information on Cpb2

• Hematological analysis of TAFI-deficient mice did not show any major differences including plasma fibrinogen level, prothrombin time, and activated partial thromboplastin time [3].
• Furthermore, TAFI deficiency did not alter kaolin-induced writhing response, implying that TAFI does not play a major role in bradykinin catabolism [3].
• Thrombin-activatable fibrinolysis inhibitor (TAFI) is a strong suppressor of fibrinolysis, but its role in lung fibrosis is unknown [4].
• Therefore, we compared bleomycin-induced lung fibrosis in TAFI-deficient, heterozygous, and wild-type mice [4].
• We generated proCPR-deficient mice by knocking out exons 4 and 5 of the proCPR gene, which are regarded as essential for CPR function [7].

Chemical compound and disease context of Cpb2

• Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis [4].

Biological context of Cpb2

• Thrombin-activatable fibrinolysis inhibitor (TAFI) is a circulating carboxypeptidase B-type proenzyme that, after activation, removes carboxyterminal lysine or arginine residues in fibrin, resulting in decreased plasminogen activation and attenuated fibrinolysis [2].
• The deduced amino acid sequence revealed that murine TAFI is highly identical to human TAFI [8].
• We have reported the elevated levels of plasma TAFI and their correlation with visceral fat area and insulin resistance in the patients with type 2 diabetes [9].
• These data suggested that the gene expression of TAFI was regulated by PI3 kinase signaling pathway [9].
• Protection could be demonstrated on the basis of leukocyte counts, colony forming unit (CPU) kinetics in liver, spleen, kidney and peritoneal cavity, and phagocytosis by monocyte-derived macrophages [10].

Anatomical context of Cpb2

• To evaluate this hypothesis, we examined the regulation of TAFI expression by insulin in adipocytes [9].
• Furthermore, the expression of TAFI was demonstrated in adipose tissues [9].

Associations of Cpb2 with chemical compounds

• Carboxypeptidase R (EC 3.4.17.20; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity [1].
• Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, after activation, can attenuate plasmin-mediated fibrin degradation by removing the C-terminal lysine residues from fibrin, which play a role in the binding and activation of plasminogen [11].

Regulatory relationships of Cpb2

• Moreover, activated Akt induced the expression of TAFI mRNA to a similar extent by insulin in 3T3-L1 adipocytes expressing tamoxifen-regulatable Akt [9].

Other interactions of Cpb2

• Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation [1].
• Insulin enhanced thrombin-activable fibrinolysis inhibitor expression through PI3 kinase/Akt pathway [9].

Analytical, diagnostic and therapeutic context of Cpb2

• Bioassay showed that the CPU value of AngP1 was 0.01 microg/body ( approximately 30 mg) for the excitatory insect toxicity and 43.0% inhibition efficiency for analgesia at a dose of 5 mg/kg [12].

References