Protection against oxidant-mediated lysosomal rupture: a new anti-apoptotic activity of Bcl-2?
Bcl-2 antagonizes apoptosis through mechanisms which are not completely understood. We have proposed that apoptosis is initiated by minor lysosomal destabilization followed some time later by secondary massive lysosomal rupture. In J774 cells over-expressing Bcl-2, early oxidant-induced lysosomal destabilization is unaffected but secondary lysosomal rupture and apoptosis are suppressed, despite the fact that wild-type and Bcl-2 over-expressing cells degrade hydrogen peroxide at similar rates. It may be that Bcl-2 directly blocks the effects of released lysosomal enzymes and/or prevents downstream activation of unknown cytosolic pro-enzymes by released lysosomal hydrolases, suggesting a new and heretofore unknown activity of Bcl-2.
Zhao
M
M
Division of Pathology II, Faculty of Health Sciences, Linköping University, Sweden.
Eaton
J W
JW
Brunk
U T
UT
D000165:Acridine Orange / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D003676:Deferoxamine / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006867:Hydrolases / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D051379:Mice; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D006861:Hydrogen Peroxide; D006867:Hydrolases; D000165:Acridine Orange; D003676:Deferoxamine