The role of the death-associated protein Daxx in modulation of apoptosis induced in cardiac myocytes by oxidative stress was studied. Exposure of cultured cardiomyocyte-like cells to oxidative stress or simulated hypoxia increased the level of accumulated ROS and apoptosis. Under conditions of sub-apoptotic stimulation of cardiac myocytes, there was no increase in the level of the Daxx protein, but it translocated from the nucleus to the cytoplasm. Daxx overexpression protected the cells from apoptosis, while they were sensitised to cell death following its down-regulation by siRNA. Moreover, lowering the level of the Daxx protein sensitised cardiac myocytes to spontaneous apoptosis, suggesting that the protein may also have a pro-survival role under physiological conditions. Finally, it was shown that DJ-1, a protein suggested previously to sequester Daxx in the nucleus under conditions of oxidative stress (thereby preventing its cytosolic translocation), was localised solely in the cytoplasm of cardiac myocytes. This indicates that the protein does not modulate the apoptosis regulatory activity of Daxx in cardiac myocytes by its nuclear sequestration. Taken together, Daxx plays a protective role in cultured cardiomyocyte-like cells, at least under the conditions used.

中文翻译：

---

Daxx抑制应激诱导的心肌细胞凋亡。

研究了死亡相关蛋白Daxx在氧化应激诱导的心肌细胞凋亡调控中的作用。将培养的心肌样细胞暴露于氧化应激或模拟的缺氧会增加ROS的积累水平和细胞凋亡。在心肌细胞亚凋亡刺激的条件下，Daxx蛋白的水平没有增加，但从核转移到细胞质。Daxx过表达保护细胞免于凋亡，而在siRNA下调细胞后，它们对细胞死亡敏感。此外，降低Daxx蛋白使心肌细胞对自发凋亡的敏感性降低，表明该蛋白在生理条件下也可能具有促生存作用。最后证明DJ-1 以前建议在氧化应激条件下将Daxx螯合在细胞核中的蛋白质（从而防止其胞质移位）仅局限在心肌细胞的细胞质中。这表明该蛋白不会通过其核螯合作用来调节Daxx在心肌细胞中的凋亡调控活性。总之，至少在所使用的条件下，Daxx在培养的心肌样细胞中起保护作用。