DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way
DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way
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DNA 损伤、死亡受体激活和活性氧是紫外线辐射诱导细胞凋亡的基本和独立方式
DOI：
10.1038/sj.onc.1205743
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发表时间：
2002-08-29
期刊：
影响因子：
8
通讯作者：
Schwarz, T
中科院分区：
文献类型：
--
作者：
Kulms, D;Zeise, E;Schwarz, T
核DNA损伤和死亡受体（CD95）在紫外线b辐射（UVB）诱导的细胞凋亡中起重要作用。去除DNA损伤并抑制死亡受体激活导致细胞凋亡明显但不完全的抑制，这表明有第三种独立的途径参与其中。由于活性氧（ROS）可引起细胞凋亡并受到UVB的诱导，因此采用了自由基清除剂吡咯烷-二硫代氨基甲酸酯（PDTC）。PDTC对uvb诱导的细胞凋亡有部分抑制作用，对h2o2诱导的细胞死亡有很大抑制作用，但对cd95介导的细胞凋亡没有抑制作用。细胞色素c从线粒体释放也是如此，这是细胞凋亡过程中的另一个重要事件。促凋亡蛋白Bid在暴露于UVB或激动性抗cd95抗体时被切割，但不被H2O2切割，表明H2O2使用不同的途径。PDTC既不抑制cd95介导的细胞凋亡，也不影响紫外线诱导的DNA损伤，这表明UVB照射时产生的ROS可能直接触发线粒体细胞色素c的释放，从而促进细胞凋亡。因此，除了通过光活化去除DNA损伤和caspase-8抑制剂zIETD阻断CD95信号外，在UVB暴露前添加PDTC可以完全抑制细胞凋亡。这表明DNA损伤、死亡受体激活和ROS的形成是uvb诱导细胞凋亡的重要和独立的途径。
Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage combined with inhibition of death receptor activation resulted in pronounced but not complete suppression of apoptosis, indicating that a third independent pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was used. PDTC prevented UVB-induced apoptosis partially, H2O2-induced cell death largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c release from mitochondria, another important event during apoptosis. The proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti-CD95-antibodies, but not to H2O2, indicating that H2O2 uses a different pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor affected UV-induced DNA damage indicated that ROS generated during UVB irradiation may directly trigger mitochondrial cytochrome c release, thereby contributing to apoptosis. Accordingly, complete inhibition of apoptosis was observed when in addition to DNA damage removal via photoreactivation and blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before UVB exposure. This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way.