Gowda C D Raghavendra, Nataraju A, Rajesh R, Dhananjaya B L, Sharath B K, Vishwanath B S
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore-570 006, Karnataka State, India.
Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jul;143(3):295-302. doi: 10.1016/j.cbpc.2006.03.001. Epub 2006 Apr 19.
The action of venom proteases and their role in hemostasis has been compared in the venoms of Trimeresurus malabaricus, Daboia russellii and Naja naja from the Southern region of Western Ghats, India. These venoms exhibit varying amounts of proteolytic activity and also influence hemostasis differently. Casein hydrolyzing activity of T. malabaricus venoms was 16 and 24 fold higher than those of N. naja and D. russellii venoms, respectively. With the synthetic substrate TAME, the highest activity was observed in T. malabaricus venom. N. naja venom did not hydrolyze TAME even at higher concentrations. These variations in proteolytic activity also influenced the coagulation process. T. malabaricus and D. russellii venoms are strongly procoagulant and reduce the re-calcification time from 148 to 14 and 12 s, respectively. Similarly, both T. malabaricus and D. russellii venoms reduce the prothrombin time from 12.5 to 6.0 s. On the other hand, N. naja venom is anticoagulant and prolongs re-calcification time to 600 s and prothrombin time to 42 s. In spite of varied effects on hemostasis, all the venoms hydrolyze fibrinogen. T. malabaricus venom hydrolyses both Aalpha and Bbeta subunits. While D. russellii and N. naja venoms hydrolyse only Aalpha. None of these venoms hydrolyze the gamma subunit of fibrinogen. Inhibition studies with specific protease inhibitors revealed that both N. naja and T. malabaricus venoms contain only metalloproteases. D. russellii venom contained both serine and metalloproteases. Only, T. malabaricus venom exhibited thrombin-like activity and induces fibrin clot formation with purified fibrinogen within 58 s. Even though D. russellii venom exhibits procoagulant activity, it did not show thrombin-like activity and may act on other coagulation factors.
对印度西高止山脉南部地区的竹叶青蛇、锯鳞蝰蛇和眼镜蛇毒液中的蛋白酶活性及其在止血过程中的作用进行了比较。这些毒液表现出不同程度的蛋白水解活性，对止血的影响也各不相同。竹叶青蛇毒液的酪蛋白水解活性分别比眼镜蛇毒液和锯鳞蝰蛇毒液高16倍和24倍。对于合成底物对甲苯磺酰-L-精氨酸甲酯（TAME），竹叶青蛇毒液的活性最高。即使在高浓度下，眼镜蛇毒液也不能水解TAME。这些蛋白水解活性的差异也影响了凝血过程。竹叶青蛇毒液和锯鳞蝰蛇毒液具有很强的促凝作用，分别将再钙化时间从148秒缩短至14秒和12秒。同样，竹叶青蛇毒液和锯鳞蝰蛇毒液都将凝血酶原时间从12.5秒缩短至6.0秒。另一方面，眼镜蛇毒液具有抗凝作用，将再钙化时间延长至600秒，凝血酶原时间延长至42秒。尽管对止血有不同影响，但所有毒液都能水解纤维蛋白原。竹叶青蛇毒液能水解Aα和Bβ亚基。而锯鳞蝰蛇毒液和眼镜蛇毒液仅能水解Aα。这些毒液均不能水解纤维蛋白原的γ亚基。用特异性蛋白酶抑制剂进行的抑制研究表明，眼镜蛇毒液和竹叶青蛇毒液仅含金属蛋白酶。锯鳞蝰蛇毒液同时含有丝氨酸蛋白酶和金属蛋白酶。只有竹叶青蛇毒液表现出类凝血酶活性，并能在58秒内用纯化的纤维蛋白原诱导纤维蛋白凝块形成。尽管锯鳞蝰蛇毒液具有促凝活性，但它没有表现出类凝血酶活性，可能作用于其他凝血因子。
