Induction of cell death by the lysosomotropic detergent MSDH

FEBS Letters

Dalen, Helge³  Firestone, Raymond A.¹  Yuan, XiMing²  Brunk, Ulf T.²  Li, Wei²  Nordgren, Gunnar²  Dubowchik, Gene M.⁴ 

[1] Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA;Division of Pathology II, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden;Department of Pathology, The Gade Institute, University of Bergen, Bergen, Norway;Pharmaceutical Research Institute, Bristol-Myers Squibb, Wallingford, CT, USA

关键词: Apoptosis;    Lysosome;    Lysosomotropic detergent;    Macrophage;    Mitochondrion;    Necrosis;   

DOI  :  10.1016/S0014-5793(00)01286-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown