Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation. CPN, however, previously termed kininase I and anaphylatoxin inactivator, is present in a stable active form in plasma. We report here the isolation of mouse proCPR and CPN cDNA clones that can induce their respective enzymatic activities in culture supernatants of transiently transfected cells. Potato carboxypeptidase inhibitor can inhibit carboxypeptidase activity in culture medium of mouse proCPR-transfected cells. The expression of proCPR mRNA in murine liver is greatly enhanced following LPS injection, whereas CPN mRNA expression remains unaffected. Furthermore, the CPR activity in plasma increased 2-fold at 24 h after LPS treatment. Therefore, proCPR can be considered a type of acute phase protein, whereas CPN is not. 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. In view of the ability of proCPR to also inhibit fibrinolysis, an excess of proCPR induced by LPS may contribute to hypofibrinolysis in patients suffering from disseminated intravascular coagulation caused by sepsis.
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PMID:Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not. 1087 83

Carboxypeptidase R (CPR) exists in precursor form (proCPR) in plasma in contrast to carboxypeptidase N (CPN), which is present in the active state. CPR plays two important roles, one of which appears to be the control of the inflammatory response by inactivation of anaphylatoxins such as complement-derived C3a and C5a. Therefore, an increase in CPR activity may facilitate rapid inactivation of these inflammatory mediators generated at the site of bacterial infection. Upregulation of proCPR expression during the inflammatory response initiated for instance by endotoxin (lipopolysaccharide) should play a role in suppressing hyper-reactivity as seen in septic shock. CPR also functions as an inhibitor of fibrinolysis, where its ability to prevent binding of plasminogen to lysine residues on fibrin clots significantly lengthens tissue plasminogen activator (tPA)-induced fibrinolysis time. Therefore, upregulation of proCPR production during the inflammatory response may exacerbate thrombosis contributing to the development of disseminated intravascular coagulation as well as other conditions involving thrombosis. Co-administration of tPA and a specific inhibitor of CPR, such as potato carboxypeptidase inhibitor, which does not affect CPN, may be useful in thrombolytic therapy.
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PMID:Carboxypeptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis. 1141 58