Wang Hua-Qin, Du Zhen-Xian, Liu Bao-Qin, Gao Yan-Yan, Meng Xin, Guan Yifu, Zhang Hai-Yan
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
FEBS Lett. 2009 May 6;583(9):1511-5. doi: 10.1016/j.febslet.2009.04.009. Epub 2009 Apr 11.
TNF-related apoptosis-inducing ligand (TRAIL) is currently considered a promising target for developing anti-cancer therapies. Accumulating evidences have now shown that oxidative stress is involved in the TRAIL-mediated cell death. The peroxiredoxins (PRDXs) are a ubiquitous family of proteins involved in protection against oxidative stress through the detoxification of cellular peroxides. Here we demonstrated that endogenous expression of PRDX4 was significantly decreased by TRAIL at the transcriptional level. In addition, overexpression of PRDX4 dramatically suppressed TRAIL-induced apoptosis. Taken together, these data for the first time suggested that TRAIL suppressed the PRDX4 gene at the transcriptional level and that downregulation of PRDX4 might facilitate cell death induced by TRAIL.
肿瘤坏死因子相关凋亡诱导配体(TRAIL)目前被认为是开发抗癌疗法的一个有前景的靶点。越来越多的证据表明,氧化应激参与了TRAIL介导的细胞死亡。过氧化物酶(PRDXs)是一类普遍存在的蛋白质家族,通过清除细胞内过氧化物来保护细胞免受氧化应激。在此我们证明,TRAIL在转录水平上显著降低了PRDX4的内源性表达。此外,PRDX4的过表达显著抑制了TRAIL诱导的细胞凋亡。综上所述,这些数据首次表明TRAIL在转录水平上抑制PRDX4基因,且PRDX4的下调可能促进TRAIL诱导的细胞死亡。