A neurotoxic secretory phospholipase A2 induces apoptosis in motoneuron-like cells.

Ammodytoxin A (AtxA) is a presynaptically neurotoxic secretory phospholipase A(2) from snake venom. The aim of this study was to investigate the mechanism of its cytotoxicity expressed against mouse motoneuronal NSC34 cells. AtxA displayed a potent dose- and time-dependent cytotoxicity that was associated with apoptosis and not necrosis, as revealed by a reduction of mitochondrial membrane potential, activation of caspase-3, and by the absence of propidium iodide staining. The cytotoxic- and apoptosis-inducing effects of AtxA were specific for the motoneuronal cells; human embryonic kidney (HEK293) and mouse myoblast (C2C12) cells were shown to be resistant to the toxin.