A major phospholipase A(2) from Daboia russelii russelii venom shows potent anticoagulant action via thrombin inhibition and binding with plasma phospholipids

作者：Mukherjee Ashis K^*

来源：Biochimie, 2014, 99C: 153-161.

DOI：10.1016/j.biochi.2013.11.026

• Russell's viper
• Phospholipase A(2)
• Thrombin inhibition
• Anticoagulant
• Neutralization
• Anticancer

This is the first report on antithrombin effects of a phospholipase A(2) (RVAPLA(2)) purified from venom of Daboia russelii russelii. The N-terminal sequence as well as in-gel tryptic digested peptides of RVAPLA(2) showed significant homology with PLA(2)s from Russell's viper venom. RVAPLA(2) demonstrated highest specific activity in hydrolyzing phosphatidylcholine (1.8 x 10(6) U/mg) with K-m and V-max values of 0.61 mM and 132.3 mu mol/min, respectively. RVAPLA(2) exerted dose dependent catalytic and strong anticoagulant activities; however, studies indicated dissociation of its catalytic and anticoagulant sites. The anticoagulant action of RVAPLA(2) was partially contributed by catalytic hydrolysis of plasma phospholipids. RVAPLA(2) showed strong anticoagulant effect via thrombin inhibition with a K-i value of 380 nM as well as by binding to pro-coagulant phospholipids of plasma. In ex-vivo conditions, RVAPLA(2) (1.0 mu M) was non-hemolytic and non-cytotoxic to mammalian cells. It did not inhibit the collagen-induced aggregation of platelets. RVAPLA(2) at a dose of 5 mg/kg was not lethal to mice after 48 h of injection. It demonstrated in vivo anticoagulant activity possibly due to targeting thrombin and binding with plasma phospholipids.

• 出版日期2014-4