Mitochondria-derived oxidative stress induces a heat shock protein response
Mitochondria-derived oxidative stress induces a heat shock protein response
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DOI：
10.1002/jnr.20249
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发表时间：
2004-11-01
影响因子：
4.2
通讯作者：
Swerdlow, RH
中科院分区：
文献类型：
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作者：
Barrett, MJ;Alones, V;Swerdlow, RH
除了减少天然和非天然蛋白聚集外，热休克蛋白（HSPs）还调节程序性细胞死亡途径。这个保守蛋白家族的成员通常被氧化应激激活，并可能有助于在这种应激条件下保持活力。为了进一步了解热休克蛋白生理学，我们研究了氧化应激的特定亚型，即由线粒体电子传递链抑制引起的氧化应激是否诱导热休克蛋白反应。我们将人类畸胎癌（NT2）细胞暴露于不同浓度的细胞色素氧化酶抑制剂叠氮化钠。微摩尔暴露导致可诱导的Hsp70和Hsp40的细胞质向细胞核易位，随后是整体上调。这种反应并不与叠氮化物暴露的开始时间一致，而是在细胞色素氧化酶抑制的程度（随着时间的推移）超过阈值时被激活。叠氮化物不影响缺乏功能性电子传递链的NT2 rho0细胞的Hsp70或Hsp40动力学。对于叠氮化物暴露的天然细胞系，在培养基中添加抗氧化剂trolox可以消除Hsp70/Hsp40的易位和上调。我们得出结论，线粒体电子传递链功能障碍激活热休克蛋白反应，而这种反应是由氧化应激介导的。(C) 2004 Wiley-Liss, Inc。
In addition to minimizing native and non-native protein aggregations, heat shock proteins (HSPs) regulate programmed cell death pathways. Members of this conserved protein family are in general activated by oxidative stress, and likely help maintain viability under this stress condition. To further our understanding of heat shock protein physiology, we studied whether a specific subtype of oxidative stress, namely that arising from mitochondrial electron transport chain inhibition, induced a heat shock protein response. We exposed human teratocarcinoma (NT2) cells to varying concentrations of the cytochrome oxidase inhibitor sodium azide. Micromolar exposures resulted in a cytoplasm to nucleus translocation of the inducible Hsp70 and of Hsp40, and this was followed by an overall upregulation. The response did not coincide temporally with the onset of azide exposure, but rather was activated when the degree of cytochrome oxidase inhibition (which was progressive over time) surpassed a threshold. Azide did not affect either Hsp70 or Hsp40 dynamics in NT2 rho0 cells, which lack functional electron transport chains. For the azide-exposed native cell line, addition of the antioxidant trolox to the medium abrogated both Hsp70/Hsp40 translocation and upregulation. We conclude that mitochondrial electron transport chain dysfunction activates a heat shock protein response, and that this response is mediated by oxidative stress. (C) 2004 Wiley-Liss, Inc.