Kim Kyung Soon, Hwang Hyun-Ah, Chae Suhn-Kee, Ha Hyunjung, Kwon Ki-Sun
Center for Systems Biology, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-333, Korea.
J Cell Biochem. 2005 Oct 1;96(2):330-8. doi: 10.1002/jcb.20545.
Oxidative stress induces apoptosis in a variety of cell types by as yet unclear signaling mechanisms. The Daxx protein is reportedly involved in apoptosis through its interactions with Fas, transforming growth factor-beta receptor, and promyelocytic leukemia protein (PML). Here, we explored the possible roles of Daxx in oxidative stress-induced apoptosis. We found that both the mRNA and protein levels of Daxx markedly increased when cells underwent apoptosis after H2O2 treatment. Pretreatment with the cell-permeable antioxidant, N-acetyl cysteine, prevented cells from H2O2-induced Daxx upregulation and subsequent apoptosis, indicating that the endogenous oxidant regulated Daxx expression. Furthermore, suppression of endogenous Daxx expression by antisense oligonucleotide technology inhibited oxidative stress-induced apoptosis in HeLa cells. Taken together, these results suggest that Daxx acts as an intermediary messenger of pro-apoptotic signals triggered by oxidative stress.
氧化应激通过尚不清楚的信号机制在多种细胞类型中诱导细胞凋亡。据报道，Daxx蛋白通过与Fas、转化生长因子-β受体和早幼粒细胞白血病蛋白（PML）相互作用参与细胞凋亡。在此，我们探讨了Daxx在氧化应激诱导的细胞凋亡中的可能作用。我们发现，当细胞在H2O2处理后发生凋亡时，Daxx的mRNA和蛋白水平均显著增加。用细胞可渗透的抗氧化剂N-乙酰半胱氨酸预处理可防止细胞发生H2O2诱导的Daxx上调及随后的凋亡，表明内源性氧化剂调节Daxx表达。此外，通过反义寡核苷酸技术抑制内源性Daxx表达可抑制HeLa细胞中氧化应激诱导的细胞凋亡。综上所述，这些结果表明Daxx作为氧化应激触发的促凋亡信号的中间信使发挥作用。
