Differential regulation of P53 and Bcl-2 expression by ultraviolet A and B.
Differential regulation of P53 and Bcl-2 expression by ultraviolet A and B.
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DOI：
10.1046/j.1523-1747.1998.00319.x
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发表时间：
1998-09
期刊：
影响因子：
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通讯作者：
Y. Wang;B. Rosenstein;S. Goldwyn;X Zhang-;M. Lebwohl;H. Wei
中科院分区：
文献类型：
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作者：
Y. Wang;B. Rosenstein;S. Goldwyn;X Zhang-;M. Lebwohl;H. Wei
紫外线（UV）辐射和其他DNA损伤剂诱导细胞凋亡在监测遗传损伤的积累和抑制肿瘤发展中起着关键作用。我们假设UVA和UVB通过调节p53和/或bcl-2基因之间的平衡来诱导细胞凋亡。使用表达野生型P53和Bcl-2蛋白的MCF-7细胞，我们证明了UVA和UVB通过调节凋亡促进或抑制基因的表达来诱导凋亡。UVA可诱导细胞凋亡，下调bcl-2蛋白表达。150 kJ UVA照射后4 h，Bcl-2表达下降约40%，24 h时下调幅度最大（超过70%）。剂量反应研究表明，在UVA剂量范围为50至200 kJ/m2时，观察到bcl-2表达显著降低;然而，p53水平不受UVA影响。与此相反，UVB表现出完全不同的行动比UVA的UVB实质上诱导p53的表达，但对bcl-2的表达没有影响。UVB对P53的诱导具有剂量和时间依赖性，最大表达出现在24 h后2和后4 kJ UVB照射每平方米。UVA诱导的bcl-2下调和DNA断裂发生早于UVB诱导的p53上调和DNA断裂（12-24 h）（约4 h）。结果提示UVA和UVB通过不同的机制引起细胞损伤，p53和bcl-2表达的平衡可能在调节UV诱导的细胞凋亡中起重要作用。
The induction of apoptosis by ultraviolet (UV) radiation and other DNA damaging agents plays a critical role in monitoring the accumulation of genetic damage and the suppression of tumor development. We hypothesize that UVA and UVB induce apoptosis by modulating balances between p53 and/or bcl-2 genes. Using MCF-7 cells that express both wild-type P53 and Bcl-2 proteins, we demonstrated that UVA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. UVA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by approximately 40% at 4 h post-150 kJ UVA irradiation per m2 with a maximum downregulation (over 70%) at 24 h. The dose-response studies revealed that significant reduction of bcl-2 expression was observed at UVA doses ranging from 50 to 200 kJ per m2; however, p53 levels were not affected by UVA. In contrast, UVB exhibited a entirely different action than UVA in that UVB substantially induced p53 expression, but had no effect on bcl-2 expression. The induction of P53 by UVB was dose and time dependent with the maximum expression at 24 h post-2 and post-4 kJ UVB irradiation per m2. Down-regulation of bcl-2 and fragmentation of DNA induced by UVA occurred earlier (approximately at 4 h) than upregulation of p53 and DNA fragmentation by UVB (12-24 h). These results suggest that UVA and UVB cause cell damage through different mechanisms and that the balances between the expression of p53 and bcl-2 may play an important role in regulating the apoptosis induced by UV irradiation.