Doley Robin, Mukherjee Ashis Kumar
Department of Molecular Biology and Biotechnology, Tezpur University, 784028, Tezpur, India.
Toxicon. 2003 Jan;41(1):81-91. doi: 10.1016/s0041-0101(02)00213-1.
An anticoagulant, non-toxic phospholipase A(2) was isolated from the venom of Indian monocled cobra (Naja kaouthia) by a combination of ion-exchange chromatography on CM-Sephadex C-50 and gel filtration on Sephadex G-50. This purified protein named NK-PLA(2)-I, had a subunit molecular mass of 13.6 kDa and migrated as a dimer under non-reduced condition in SDS-PAGE. NK-PLA(2)-I was a highly thermostable protein requiring basic pH optima for its catalytic activity and showed preferential hydrolysis of phosphotidylcholine. This protein exhibited higher anticoagulant, indirect hemolysis, liver and heart tissue damaging activity but exerted less toxicity, direct hemolysis, edema and lung tissue damaging activity as compared to whole venom. Treatment of NK-PLA(2)-I with rho-BPB, TPCK, PMSF, antivenom and heating had almost equal effect on PLA(2), and other pharmacological properties except in vitro tissue damaging activity. Current investigation provides a fairly good indication that NK-PLA(2)-I induces various pharmacological effects by mechanisms, which are either dependent or independent of its catalytic activity.
通过在CM - Sephadex C - 50上进行离子交换色谱和在Sephadex G - 50上进行凝胶过滤相结合的方法,从印度单眼眼镜蛇(眼镜王蛇)的毒液中分离出一种抗凝、无毒的磷脂酶A(2)。这种纯化的蛋白质名为NK - PLA(2)-I,其亚基分子量为13.6 kDa,在SDS - PAGE的非还原条件下以二聚体形式迁移。NK - PLA(2)-I是一种高度耐热的蛋白质,其催化活性需要碱性最适pH值,并表现出对磷脂酰胆碱的优先水解作用。与全毒液相比,该蛋白质表现出更高的抗凝、间接溶血、肝脏和心脏组织损伤活性,但毒性、直接溶血、水肿和肺组织损伤活性较低。用rho - BPB、TPCK、PMSF、抗蛇毒血清和加热处理NK - PLA(2)-I对PLA(2)和其他药理特性几乎有相同的影响,但体外组织损伤活性除外。目前的研究提供了一个相当好的迹象,即NK - PLA(2)-I通过依赖或不依赖其催化活性的机制诱导各种药理作用。