Non-covalent interaction of phospholipase A(2) (PLA(2)) and kaouthiotoxin (KTX) from venom of Naja kaouthia exhibits marked synergism to potentiate their cytotoxicity on target cells.

Abstract

Present study shows that non-covalent interaction of kaouthiotoxin (KTX) with their respective pohospholipase A(2) (PLA(2)) from the venom of N. kaouthia displayed marked synergism to exert cytotoxicity without altering the biochemical properties of PLA(2). For example, although NK-PLA(2) or KTX alone did not induce appreciable hemolysis of washed human erythrocytes; however, the hemolytic potency of NK-PLA(2): KTX complex was significantly higher. Identically, selective lysis of virus infected Sf9 and normal Tn insect cells was further enhanced by the cognate NK-PLA(2): KTX complex as compared to individual components of the complex. Gas-chromatographic analysis of fatty acids released from intact erythrocytes by cytotoxic action of individual NK-PLA(2) and NK-PLA(2): KTX complex demonstrated that ratio between saturated fatty acids (SFA) and unsaturated FA (UFA) was increasing with time of hydrolysis of RBC either in the case of NK-PLA(2) or NK-PLA(2)-KTX complex suggesting NK-PLA(2)-KTX complex apparently displayed the more preference for glycerophospholipids with SFAs on the sn-2 position. Therefore, it may be suggested that KTX first destabilize the target cell membrane followed by higher enzymatic activity of PLA(2) on dislocated and disorganized phospholipid bilayers resulting in a significantly higher (p < 0.05) membrane damage by NK-PLA(2)-KTX complex compared to individual components of the complex.