Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes
Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes
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DOI：
10.1074/jbc.m600536200
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发表时间：
2006-06-30
影响因子：
4.8
通讯作者：
de Verneuil, Hubert
中科院分区：
文献类型：
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作者：
Rezvani, Hamid Reza;Mazurier, Frederic;de Verneuil, Hubert
紫外线诱导角质形成细胞的凋亡是一个高度复杂的过程，涉及多种分子途径。这些途径包括通过触发死亡受体的外在途径和通过DNA损伤和活性氧物种(ROS)形成的内在途径。在本研究中，我们研究了过氧化氢酶和铜锌超氧化物歧化酶的过表达对常温和4℃中波紫外线照射诱导的正常人角质形成细胞凋亡的影响。低温照射可将紫外线诱导的正常角质形成细胞的凋亡率减少40%，而与P53的任何变化无关，同时caspase-8的活性降低。过氧化氢酶过表达使细胞凋亡率减少40%，同时caspase-9活性降低，同时p53蛋白表达减少。细胞低温保存和过氧化氢酶过表达具有相加效应。CuZn-SOD过表达对UVB诱导的细胞凋亡无明显影响。UVB在照射后即刻和照射后3h左右两个不同的阶段诱导ROS水平升高。过氧化氢酶过表达仅抑制后期ROS水平的升高。我们认为，过氧化氢酶过表达通过阻止晚期ROS增加所介导的DNA损伤，对UVB辐射具有保护作用。
UV-induced apoptosis in keratinocytes is a highly complex process in which various molecular pathways are involved. These include the extrinsic pathway via triggering of death receptors and the intrinsic pathway via DNA damage and reactive oxygen species (ROS) formation. In this study we investigated the effect of catalase and CuZn-superoxide dismutase (SOD) overexpression on apoptosis induced by UVB exposure at room temperature or 4 C on normal human keratinocytes. Irradiation at low temperature reduced UV-induced apoptosis by 40% in normal keratinocytes independently of any change in p53 and with a decrease in caspase-8 activation. Catalase overexpression decreased apoptosis by 40% with a reduction of caspase-9 activation accompanied by a decrease in p53. Keeping cells at low temperature and catalase overexpression had additive effects. CuZn-SOD overexpression had no significant effect on UVB-induced apoptosis. UVB induced an increase in ROS levels at two distinct stages: immediately following irradiation and around 3 h after irradiation. Catalase overexpression inhibited only the late increase in ROS levels. We conclude that catalase overexpression has a protective role against UVB irradiation by preventing DNA damage mediated by the late ROS increase.