Induction of cell death by the lysosomotropic detergent MSDH

作者：Wei Li, Xi Yuan, Gunnar Nordgren, Helge Dalen, Gene M. Dubowchik, Raymond A. Firestone, Ulf T. Brunk · 发表于：FEBS Letters · 年份：2000 · DOI：10.1016/s0014-5793(00)01286-2 · 被引用次数：244 · 研究领域：Cell death mechanisms and regulation、Autophagy in Disease and Therapy、Phagocytosis and Immune Regulation

Controlled lysosomal rupture was initiated in lysosome-rich, macrophage-like cells by the synthetic lysosomotropic detergent, O-methyl-serine dodecylamide hydrochloride (MSDH). When MSDH was applied at low concentrations, resulting in partial lysosomal rupture, activation of pro-caspase-3-like proteases and apoptosis followed after some hours. Early during apoptosis, but clearly secondary to lysosomal destabilization, the mitochondrial transmembrane potential declined. At high concentrations, MSDH caused extensive lysosomal rupture and necrosis. It is suggested that lysosomal proteases, if released to the cytosol, may cause apoptosis directly by pro-caspase activation and/or indirectly by mitochondrial attack with ensuing discharge of pro-apoptotic factors.