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char = B;code = 66
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char = .;code = 46
result sql = Caspase- and mitochondrial dysfunction-dependent mechanisms of lysosomal leakage and cathepsin B activation in DNA damage-induced apoptosis.
Caspase- and mitochondrial dysfunction-dependent mechanisms of lysosomal leakage and cathepsin B activation in DNA damage-induced apoptosis.
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result sql = A lysosomal pathway, characterized by partial rupture of lysosomal membranes and cathepsin B activation, is activated during camptothecin (CPT)-induced apoptosis in U937 and Namalwa cancer cells. These lysosomal events occur simultaneously with mitochondrial permeabilization and caspase activation. In U937 cells, blocking mitochondrial permeability transition pore with cyclosporin A and bongkrekic acid reduces mitochondrial and lysosomal rupture, suggesting that lysosomal rupture may be dependent, in part, on mitochondrial disruption. Overexpressing bcl-xL, an antiapoptotic protein known to preserve mitochondrial functions, also impedes lysosomal and mitochondrial disruption in both cell lines, indicating signaling between the two organelles. In addition, no evidence was obtained of bcl-2-like proteins targeting lysosomes. Caspase activities, including caspase-2L, are required for lysosomal and mitochondrial disruption, and lysosomal cathepsin B slightly participates in apoptosis propagation after CPT, although not essential for apoptosis activation. Our study provides evidence for the participation of a lysosomal pathway during DNA damage-induced cell death. Our data suggest that caspase activation and mitochondrial disruption represent cell-context-specific mechanisms by which DNA damage leads to lysosomal rupture, and that lysosomal cathepsins could slightly participate in apoptosis propagation after CPT.

Publication: Leukemia 2005 May ;19(5)::784-91.
Publication Date: 2005 May
Study Author(s): Paquet, C;Sané, A-T;Beauchemin, M;Bertrand, R;
Institution: Centre de recherche, Centre hospitalier de l'Université of Montréal (CHUM) -Hôpital Notre-Dame and Institut du cancer de Montréal, Canada.
Shortcut link to this study:
A lysosomal pathway, characterized by partial rupture of lysosomal membranes and cathepsin B activation, is activated during camptothecin (CPT)-induced apoptosis in U937 and Namalwa cancer cells. These lysosomal events occur simultaneously with mitochondrial permeabilization and caspase activation. In U937 cells, blocking mitochondrial permeability transition pore with cyclosporin A and bongkrekic acid reduces mitochondrial and lysosomal rupture, suggesting that lysosomal rupture may be dependent, in part, on mitochondrial disruption. Overexpressing bcl-xL, an antiapoptotic protein known to preserve mitochondrial functions, also impedes lysosomal and mitochondrial disruption in both cell lines, indicating signaling between the two organelles. In addition, no evidence was obtained of bcl-2-like proteins targeting lysosomes. Caspase activities, including caspase-2L, are required for lysosomal and mitochondrial disruption, and lysosomal cathepsin B slightly participates in apoptosis propagation after CPT, although not essential for apoptosis activation. Our study provides evidence for the participation of a lysosomal pathway during DNA damage-induced cell death. Our data suggest that caspase activation and mitochondrial disruption represent cell-context-specific mechanisms by which DNA damage leads to lysosomal rupture, and that lysosomal cathepsins could slightly participate in apoptosis propagation after CPT.
PMID: 15759029

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