Induction of apoptosis by YTX in myoblast cell lines via mitochondrial signalling transduction pathway

Abstract

Yessotoxin (YTX) can induce apoptotic events in myoblast L6 and BC3H1 cell lines from rat and mouse, respectively. The present study indicates that apoptosis induced by YTX in these cell lines can occur through activation of the mitochondrial pathway indicating an intracellular response. Terminal events during mitochondrial-mediated apoptosis involve perturbations to mitochondria resulting in loss of mitochondrial membrane potential (DeltaPsi(m)), permeability transition pore (PTP) opening and the release of proapoptotic factors cytochrome c, smac/DIABLO into the cytosol. Results from western blotting, electron and fluorescent microscopy of YTX-treated myoblast cells provided experimental data for evaluation of cytochrome c, smac/DIABLO release and caspase-9 activation. Loss of mitochondrial membrane potential and swelling of mitochondria indicated an active role of mitochondria during the early phase of apoptosis in L6 and BC3H1 cells after YTX exposure. These observations show that YTX targets mitochondria and involve activation of a cascade of events through mitochondrial regulation.