Caspase activation and disruption of mitochondrial membrane potential during UV radiation-induced apoptosis of human keratinocytes requires activation of protein kinase C
Caspase activation and disruption of mitochondrial membrane potential during UV radiation-induced apoptosis of human keratinocytes requires activation of protein kinase C
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DOI：
10.1038/sj.cdd.4400929
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发表时间：
2002-01-01
影响因子：
12.4
通讯作者：
Qin, JZ
中科院分区：
文献类型：
--
作者：
Denning, MF;Wang, Y;Qin, JZ
紫外线辐射诱导人角质形成细胞凋亡涉及半胱天冬酶介导的蛋白激酶C δ（PKC δ）的裂解和激活。在这里，我们研究了PKC激活的作用，半胱天冬酶激活和破坏线粒体功能的紫外线辐射。PKC的抑制部分阻断了UV辐射诱导的PKC δ、caspase-3和caspase-8的裂解以及这些caspase的激活。PKC抑制还阻断了UV诱导的线粒体膜电位的损失，但不阻断细胞色素c从线粒体的释放。PKC δ的活性催化结构域的表达足以诱导细胞凋亡并破坏线粒体膜电位，而激酶失活的PKC δ催化结构域不足以诱导细胞凋亡并破坏线粒体膜电位。此外，UV辐射后产生的PKC δ催化片段定位于线粒体部分，异位表达的PKC δ催化结构域也是如此。这些结果确定了PKC激活在增强caspase激活和破坏线粒体功能在紫外线诱导的细胞凋亡的功能作用。
The induction of apoptosis in human keratinocytes by UV radiation involves caspase-mediated cleavage and activation of protein kinase C delta (PKCdelta). Here we examined the role of PKC activation in caspase activation and disruption of mitochondria function by UV radiation. Inhibition of PKC partially blocked UV radiation-induced cleavage of PKCdelta, pro-caspase-3, and pro-caspase-8, and the activation of these caspases. PKC inhibition also blocked the UV-induced loss of mitochondria membrane potential, but did not block the release of cytochrome c from mitochondria, Expression of the active catalytic domain of PKCdelta was sufficient to induce apoptosis and disrupt mitochondrial membrane potential, however a kinase inactive PKCdelta catalytic domain did not, Furthermore, the PKCdelta catalytic fragment generated following UV radiation localized to the mitochondria fraction, as did ectopically expressed PKCdelta catalytic domain. These results identify a functional role for PKC activation in potentiating caspase activation and disrupting mitochondrial function during UV-induced apoptosis.