Molecular function of stress protein A170 in skin carcinogenesis by UV radiation

应激蛋白A170在紫外线辐射皮肤癌变中的分子功能

• 批准号: 21791060
• 负责人: ISHII Yoshiyuki
• 金额: $ 2.75万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791060/
• 关键词: 紫外線障害; A170; Sequestosomel; p62; アポトーシス

In this study, the role of A170 in UVB induced apoptosis was investigated. A170 is known to stress inducible gene, and A170 deficient mice show mature onset obesity. We previously found mouse embryonic fibroblast (MEF) derived from A170 KO mice were resistant to UVB induced cell death. At first, we analyzed whether A170 knocked down wild type MEF show same characters as KO MEF against UVB radiation. The results shows knockdown cells are also resistant to UVB. Next, the proteins involved in the apoptotic signal were analyzed. Interestingly, pro-apoptotic protein levels such as Bax, caspase after UVB exposure were reduced in KO cells. In addition, anti-apoptotic protein mRNA levels were markedly increased in KO cells compared with WT. We found transcription factor Stat3 which is known to positively regulates anti-apoptotic gene induction was remarkably activated in KO cells. Moreover, in vivo analysis revealed that A170 KO mice skin tissue show relatively low damage by UVB radiation. These results suggest that A170 is novel important factor for regulating apoptotic signal by altering pro- and anti-apoptotic protein levels.

在这项研究中，研究了A170在UVB诱导的凋亡中的作用。已知A170应力诱导基因，A170缺乏小鼠表现出成熟的发作肥胖。我们先前发现源自A170 KO小鼠的小鼠胚胎成纤维细胞（MEF）对UVB诱导的细胞死亡具有抗性。起初，我们分析了A170是否将野生型MEF击倒与KO MEF相同的角色对UVB辐射。结果表明敲低细胞也对UVB具有抗性。接下来，分析了参与凋亡信号的蛋白质。有趣的是，在KO细胞中，UVB暴露后的pro凋亡蛋白水平（例如BAX）降低了caspase。另外，与WT相比，KO细胞中抗凋亡蛋白mRNA水平明显增加。我们发现转录因子STAT3在KO细胞中已明显激活抗凋亡基因诱导的转录因子STAT3。此外，体内分析表明，A170 KO小鼠皮肤组织的UVB辐射损伤相对较低。这些结果表明，A170是通过改变促凋亡蛋白水平来调节凋亡信号的新重要因素。

项目成果

Essential role of Nrf2 in keratinocyte protection from UVA by quercetin

• DOI: 10.1016/j.bbrc.2009.06.136
• 发表时间: 2009-09-11
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kimura, Shintarou;Warabi, Eiji;Ishii, Tetsuro
• 通讯作者: Ishii, Tetsuro