Ultraviolet B radiation-induced apoptosis in human keratinocytes: cytosolic activation of procaspase-8 and the role of Bcl-2
Ultraviolet B radiation-induced apoptosis in human keratinocytes: cytosolic activation of procaspase-8 and the role of Bcl-2
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DOI：
10.1016/s0014-5793(03)00238-2
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发表时间：
2003-04-10
期刊：
影响因子：
3.5
通讯作者：
Agostinis, P
中科院分区：
文献类型：
--
作者：
Assefa, Z;Garmyn, M;Agostinis, P
在这项研究中，我们表明，紫外线B辐射（UVB）诱导的人类角质形成细胞凋亡主要涉及胞浆信号，其中线粒体发挥核心作用。Bcl-2的过表达通过阻断活性氧的早期产生、线粒体心磷脂降解和细胞色素c释放来抑制UVB诱导的细胞凋亡，而不影响Fas配体（FasL）诱导的细胞死亡。它还阻止了随后的激活procaspase-3和-8，以及投标切割UVB处理的细胞。UVB和FasL死亡途径的比较分析揭示了不同的作用和机制的caspase激活，与UVB诱导的caspase-8的激活只是一个旁观者的胞质事件，而不是一个主要的启动机制，是FasL诱导的细胞死亡的情况下。我们的研究结果表明，Bcl-2的过度表达，通过防止活性氧的产生，有助于间接地保持溶酶体膜的完整性，因此抑制组织蛋白酶的释放，这有助于在UVB照射的角质形成细胞中的caspase-8的胞质激活。(C)2003年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
In this study, we show, that ultraviolet B radiation (UVB)-induced apoptosis of human keratinocytes involves mainly cytosolic signals with mitochondria playing a central role. Overexpression of Bcl-2 inhibited UVB-induced apoptosis by blocking the early generation of reactive oxygen species, mitochondrial cardiolipin degradation and cytochrome c release, without affecting Fas ligand (FasL)-induced cell death. It also prevented the subsequent activation of procaspase-3 and -8 as well as Bid cleavage in UVB-treated cells. Comparative analysis of UVB and FasL death pathways revealed a differential role and mechanism of caspase activation, with the UVB-induced activation of procaspase-8 only being a bystander cytosolic event rather than a major initiator mechanism, as is the case for the FasL-induced cell death. Our results suggest that Bcl-2 overexpression, by preventing reactive oxygen species production, helps indirectly to maintain the integrity of lysosomal membranes, and therefore inhibits the release of cathepsins, which contribute to the cytosolic activation of procaspase-8 in UVB-irradiated keratinocytes. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.