Wano Chieko, Kita Kazuko, Takahashi Shunji, Sugaya Shigeru, Hino Mizuki, Hosoya Hiroshi, Suzuki Nobuo
Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Exp Cell Res. 2004 Aug 15;298(2):584-92. doi: 10.1016/j.yexcr.2004.04.048.
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.
热休克蛋白(HSPs)是否在紫外线C(UVC)诱导的人类细胞死亡中发挥保护作用是一个有趣的问题,且该问题尚未得到解决。为了寻找与UVC抗性相关的热休克蛋白,我们比较了UVC敏感的人类RSa细胞及其UVC抗性变体AP(r)-1细胞之间使用cDNA阵列的基因表达谱。热休克蛋白27(HSP27)在RSa细胞中的表达水平低于AP(r)-1细胞。用正义HSP27 cDNA转染的RSa细胞对UVC诱导的细胞死亡的敏感性略低于仅用载体转染的对照细胞,且远低于用反义HSP27 cDNA转染的RSa细胞。此外,与对照细胞相比,HSP27上调的细胞中两种主要类型的UVC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HSP27下调的细胞中的去除能力则显著受到抑制。这些结果表明,HSP27至少在我们测试的人类细胞中参与UVC抗性,可能是通过在核苷酸切除修复中发挥作用。