Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress
Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during oxidative stress
复制标题
Nucleolin/C23 在氧化应激过程中介导热休克蛋白 70 的抗凋亡作用
DOI：
10.1111/j.1742-4658.2009.07510.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.4
通讯作者：
Xiao, Xianzhong
中科院分区：
文献类型：
--
作者：
Jiang, Bimei;Zhang, Bin;Xiao, Xianzhong
虽然热休克蛋白70（Hsp70）能显著抑制H2O2诱导的C2C12细胞凋亡，核仁素/C23也参与了细胞凋亡，但这两种分子之间的关系仍不清楚。本研究的目的是探讨核仁素/C23在热休克蛋白70的抗凋亡机制的潜在参与。我们发现原代培养的新生大鼠心肌细胞在H2O2处理后发生凋亡，并且在这些细胞中核仁素/C23蛋白高度不稳定，半衰期小于4 h。然而，转染热休克蛋白70大大稳定核仁素/C23，也保护细胞免受过氧化氢诱导的凋亡。当核仁素/C23被敲低与反义寡聚体，H2O2诱导的细胞凋亡变得更加严重，即使在Hsp70过表达的细胞，证明核仁素/C23在Hsp70的抗凋亡作用的重要作用。细胞核形态学观察和caspase-3活性测定结果相似。因此，这些数据提供的证据表明，核仁素/C23是一个重要的下游效应的热休克蛋白70在保护心肌细胞免受氧化应激诱导的凋亡。
Although heat shock protein 70 (Hsp70) has been shown to markedly inhibit H2O2-induced apoptosis in C2C12 cells, and nucleolin/C23 has also been implicated in apoptosis, the relationship of these two molecules is still largely unknown. The aim of the current study was to investigate the potential involvement of nucleolin/C23 in the antiapoptotic mechanism of Hsp70. We found that primary cultures of neonatal rat cardiomyocytes underwent apoptosis upon H2O2 treatment, and in these cells nucleolin/C23 protein was highly unstable and had a half-life of less than 4 h. However, transfection with Hsp70 greatly stabilized nucleolin/C23 and also protected the cells from H2O2-induced apoptosis. When nucleolin/C23 was knocked down with an antisense oligomer, H2O2-induced apoptosis became more severe, even in Hsp70-overexpressed cells, demonstrating an essential role of nucleolin/C23 in the antiapoptotic effects of Hsp70. Similar results were obtained by both nuclear morphology observation and caspase-3 activity assay. Therefore, these data provide evidence that nucleolin/C23 is an essential downstream effecter of Hsp70 in the protection of cardiomyocytes against oxidative stress-induced apoptosis.