Induction of cell death by the lysosomotropic detergent MSDH.
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.
Li
W
W
Division of Pathology II, Faculty of Health Sciences, University of Linköping, S-581 85, Linköping, Sweden.
Yuan
X
X
Nordgren
G
G
Dalen
H
H
Dubowchik
G M
GM
Firestone
R A
RA
Brunk
U T
UT
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D003902:Detergents / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020298:U937 Cells
D000577:Amides; D003902:Detergents; C407126:O-methyl-serine dodecylamide hydrochloride; D012694:Serine; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases