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1 August 2001 Different Pathways Mediate Cytochrome c Release After Photodynamic Therapy with Hypericin
Annelies Vantieghem, Yan Xu, Wim Declercq, Peter Vandenabeele, Geertrui Denecker, Jackie R. Vandenheede, Wilfried Merlevede, Peter A. de Witte, Patrizia Agostinis
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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.

Annelies Vantieghem, Yan Xu, Wim Declercq, Peter Vandenabeele, Geertrui Denecker, Jackie R. Vandenheede, Wilfried Merlevede, Peter A. de Witte, and Patrizia Agostinis "Different Pathways Mediate Cytochrome c Release After Photodynamic Therapy with Hypericin," Photochemistry and Photobiology 74(2), 133-142, (1 August 2001). https://doi.org/10.1562/0031-8655(2001)074<0133:DPMCCR>2.0.CO;2
Received: 6 October 2000; Accepted: 1 May 2001; Published: 1 August 2001
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