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Induction of cell death by the lysosomotropic detergent MSDH
Author(s) -
Li Wei,
Yuan XiMing,
Nordgren Gunnar,
Dalen Helge,
Dubowchik Gene M.,
Firestone Raymond A.,
Brunk Ulf T.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01286-2
Subject(s) - proteases , lysosome , apoptosis , caspase , programmed cell death , microbiology and biotechnology , cytosol , cytochrome c , chemistry , necrosis , biochemistry , biology , enzyme , genetics
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.