Identification of the snake venom substance that induces apoptosis

Hemorrhagic snake venom induces apoptosis of vascular endothelial cells [S. Araki, T. Ishida, T. Yamamoto, K. Kaji, and H. Hayashi (1993) Biochem. Biophys. Res. Comm. 190 , 148-153]. We have identified that a cytotoxic substance of Korean snake venom which is responsible for the apoptosis is L-amino acid oxidase (LAO). The purified enzyme is a homodimeric glycoprotein of 110,000 and is capable of generating H2O2 by catalyzing oxidation of L-amino acid. In the presence of the enzyme, cultured L1210 cell nuclei were splitted and showed the characteristic ladder-like pattern of DNA fragmentation. The enzyme binds directly to the cell surface, thereby increasing local concentration of H2O2. However, experimental evidence suggests that the LAO-induced apoptotic mechanism is distinguished from the one caused by exogenous H2O2.