Different Pathways Mediate Cytochrome c Release After Photodynamic Therapy with Hypericin
Different Pathways Mediate Cytochrome c Release After Photodynamic Therapy with Hypericin
复制标题
金丝桃素光动力治疗后不同途径介导细胞色素 c 释放
DOI：
10.1562/0031-8655(2001)0740133dpmccr2.0.co2
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发表时间：
2001
影响因子：
3.1
通讯作者：
P. Agostinis
中科院分区：
文献类型：
--
作者：
A. Vantieghem;Yan Xu;W. Declercq;P. Vandenabeele;G. Denecker;J. Vandenheede;W. Merlevede;P. D. de Witte;P. Agostinis
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.
影响因子：
56.9
作者：
KANE, DJ;SARAFIAN, TA;BREDESEN, DE
通讯作者：
BREDESEN, DE