Protective role of HSP27 against UVC-induced cell death in human cells

Protective role of HSP27 against UVC-induced cell death in human cells
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DOI:
10.1016/j.yexcr.2004.04.048
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发表时间:
2004-08-15
影响因子:
3.7
通讯作者:
Suzuki, N
Suzuki, N
中科院分区:
医学3区
文献类型:
--
作者:
Wano, C;Kita, K;Suzuki, N

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热休克蛋白(HSPs)是否在紫外线诱导的细胞死亡中起保护作用是一个有趣的问题,至今尚未得到解决。为了寻找参与UVC抗性的热休克蛋白,使用cDNA阵列比较了UVC敏感的人RSa细胞和其UVC抗性变体AP(r)-1细胞的基因表达谱。热休克蛋白27(HSP 27)在RSa细胞中的表达水平低于AP(r)-1细胞。转染正义HSP 27 cDNA的RSa细胞对UV C诱导的细胞死亡的敏感性比单独转染载体的对照细胞稍低,而比转染反义HSP 27 cDNA的RSa细胞的敏感性低得多。此外,与对照细胞相比,HSP 27上调的细胞中的两种主要类型的UV损伤DNA(胸腺嘧啶二聚体和(6-4)光产物)的去除能力适度提高,而在下调的细胞中的去除能力被显著抑制。这些结果表明,热休克蛋白27参与人体细胞的紫外线抗性,至少是那些测试,可能通过核苷酸切除修复功能。(C)2004年爱思唯尔公司All rights reserved.
It is an intriguing problem whether heat shock proteins (HSPs) play a protective role in UVC-induced cell death in human cells, and the problem has not been solved. To search for the HSPs involved in UVC resistance, gene expression profiles using cDNA array were compared between UVC-sensitive human RSa cells and their UVC-resistant variant AP(r)-1 cells. The expression levels of heat shock protein 27 (HSP27) were lower in RSa cells than in AP(r)-1 cells. RSa cells transfected with sense HSP27 cDNA showed slightly lower sensitivity to UVC-induced cell death than the control cells transfected with a vector alone and much lower sensitivity than RSa cells transfected with the antisense HSP27 cDNA. Furthermore, the removal capacities of the two major types of UVC-damaged DNA (thymine dimers and (6-4)photoproducts) in the cells with the up-regulation of HSP27 were moderately elevated compared with those in the control cells, while those in the cells with down-regulation were remarkably suppressed. These results suggest that HSP27 is involved in the UVC-resistance of human cells, at least those tested, possibly via functioning in nucleotide excision repair. (C) 2004 Elsevier Inc. All rights reserved.