Induction of cell death by the lysosomotropic detergent MSDH

Controlled lysosomal rupture was initiated in lysosome-rich, macrophage-lik e cells by the synthetic lysosomotropic detergent, O-methyl-serine dodecyla mide hydrochloride (MSDH). When MSDH was applied at low concentrations, res ulting in partial lysosomal rupture, activation of pro-caspase-3-like prote ases and apoptosis followed after some hours. Early during apoptosis, but c learly secondary to lysosomal destabilization, the mitochondrial transmembr ane potential declined. At high concentrations, MSDH caused extensive lysos omal rupture and necrosis. It is suggested that lysosomal proteases, if rel eased to the cytosol, may cause apoptosis directly by pro-caspase activatio n and/or indirectly by mitochondrial attack with ensuing discharge of pro-a poptotic factors. (C) 2000 Federation of European Biochemical Societies.