Title: Different pathways mediate cytochrome c release after photodynamic therapy with hypericin
Authors: Vantieghem, Annelies ×
Xu, Yan
Declerck, Wim
Vandenabeele, Peter
Denecker, Geertrui
Vandenheede, Jackie
Merlevede, Wilfried
de Witte, Peter
Agostinis, Patrizia #
Issue Date: Aug-2001
Publisher: Amer soc photobiology
Series Title: Photochemistry and photobiology vol:74 issue:2 pages:133-142
Abstract: In this study we show that overexpression of Bcl-2 in PC60R1R2 cells reveals a caspase-dependent mechanism of cytochrome c release following photodynamic therapy (PDT) with hypericin. Bcl-2 overexpression remarkably delayed cytochrome c release, procaspase-3 activation and poly(adenosine diphosphate-ribose)polymerase cleavage during PDT-induced apoptosis while it did not protect against PDT-induced necrosis. PDT-treated cells showed a reduction in the mitochondrial membrane potential which occurred with similar kinetics in PC60R1R2 and PC60R1R2/Bcl-2 cells, and was affected neither by the permeability transition pore inhibitor cyclosporin A nor by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk). Hypericin-induced mitochondrial depolarization coincided with cytochrome c release in PC60R1R2 cells while it precedes massive cytochrome c efflux in PC60R1R2/Bcl-2 cells. Preincubation of PC60R1R2 cells with zVAD-fmk or cyclosporin A did not prevent the mitochondrial efflux of cytochrome c, and caspase inhibition only partially protected the cells from PDT-induced apoptosis. In contrast, in PC60R1R2/Bcl-2 cells cytochrome c release and apoptosis were suppressed by addition of zVAD-fmk or cyclosporin A. These observations suggest that the progression of the PDT-induced apoptotic process in Bcl-2-overexpressing cells involves a caspase-dependent feed-forward amplification loop for the release of cytochrome c.
ISSN: 0031-8655
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Protein Phosphorylation and Proteomics
Laboratory for Pharmaceutical Biology (-)
Biochemistry Section (Medicine) (-)
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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