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Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV,〔〔 is a zymogen, the activated form of which plays an important role in regulating anticoagulation, inflammation, cell death, and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease as it contains a residue of serine in its active site.〔 In humans, protein C is encoded by the ''PROC'' gene, which is found on chromosome 2.〔 The zymogenic form of protein C is a vitamin K-dependent glycoprotein that circulates in blood plasma. Its structure is that of a two-chain polypeptide consisting of a light chain and a heavy chain connected by a disulfide bond.〔 The protein C zymogen is activated when it binds to thrombin, another protein heavily involved in coagulation, and protein C's activation is greatly promoted by the presence of thrombomodulin and endothelial protein C receptors (EPCRs). Because of EPCR's role, activated protein C is found primarily near endothelial cells (i.e., those that make up the walls of blood vessels), and it is these cells and leukocytes (white blood cells) that APC affects.〔〔 Because of the crucial role that protein C plays as an anticoagulant, those with deficiencies in protein C, or some kind of resistance to APC, suffer from a significantly increased risk of forming dangerous blood clots (thrombosis). Research into the clinical use of activated protein C also known as drotrecogin alfa-activated (branded Xigris) has been surrounded by controversy. The manufacturer Eli Lilly and Company ran an aggressive marketing campaign to promote its use in people with severe sepsis and septic shock including the sponsoring of the 2004 Surviving Sepsis Campaign Guidelines. A 2011 Cochrane review however found that its use cannot be recommended as it does not improve survival (and increases bleeding risk). ==History== Protein C's anticoagulant role in the human body was first noted by Seegers ''et al.'' in 1960,〔 who gave protein C its original name, ''autoprothrombin II-a''.〔 Protein C was first isolated by Johan Stenflo from bovine plasma in 1976, and Stenflo determined it to be a vitamin K-dependent protein.〔 He named it protein ''C'' because it was the third protein ("peak C") that eluted from a DEAE-Sepharose ion-exchange chromotograph. Seegers was, at the time, searching for vitamin K-dependent coagulation factors undetected by clotting assays, which measure global clotting function. Soon after this, Seegers recognised Stenflo's discovery was identical with his own.〔 Activated protein C was discovered later that year,〔 and in 1977 it was first recognised that APC inactivates Factor Va.〔〔 In 1980, Vehar and Davie discovered that APC also inactivates Factor VIIIa,〔 and soon after, Protein S was recognised as a cofactor by Walker.〔 In 1982, a family study by Griffin ''et al''. first associated protein C deficiency with symptoms of venous thrombosis.〔 Homozygous protein C deficiency and the consequent serious health effects were described in 1984 by several scientists.〔 cDNA cloning of protein C was first performed in 1984 by Beckmann ''et al.'' which produced a map of the gene responsible for producing protein C in the liver.〔 In 1987 a seminal experiment was performed (Taylor ''et al.'') whereby it was demonstrated that activated protein C prevented coagulopathy and death in baboons infused with lethal concentrations of ''E. coli.''〔〔 In 1993, a heritable resistance to APC was detected by Dahlbäck ''et al.'' and associated with familial thrombophilia.〔 In 1994, the relatively common genetic mutation that produces Factor VLeiden was noted (Bertina ''et al.'').〔 Two years later, Gla-domainless APC was imaged at a resolution of 2.8 Ångströms.〔 Beginning with the PROWESS clinical trial of 2001,〔 it was recognised that many of the symptoms of sepsis may be ameliorated by infusion of APC, and mortality rates of septic patients may be significantly decreased.〔 Near the end of that year, Drotrecogin alfa (activated), a recombinant human activated protein C, became the first drug approved by the U.S. FDA for treating severe sepsis.〔 In 2002, ''Science'' published an article that first showed protein C activates protease-activated receptor-1 (PAR-1) and this process accounts for the protein's modulation of the immune system.〔〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Protein C」の詳細全文を読む スポンサード リンク
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