Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.

Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.
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与热应激,氧化应激和果蝇果蝇的电离辐射相比,基因表达对衰老的反应发生了变化。

DOI:
10.18632/aging.100499
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发表时间:
2012-11
期刊:
Aging
影响因子:
--
通讯作者:
Tower J
Tower J
中科院分区:
其他
文献类型:
--
作者:
Landis G;Shen J;Tower J

文献摘要

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基因表达的变化,响应老化,热应激,高氧,过氧化氢,电离辐射进行了比较,使用微阵列。一组18个基因在所有条件下均上调,表明与衰老共有的一般应激反应,包括热休克蛋白(Hsp)基因Hsp 70、Hsp 83和I(2)efl,谷胱甘肽-S-转移酶基因GstD 2和线粒体未折叠蛋白反应(mUPR)基因ref(2)P。使用定量PCR确认选定的基因表达变化,北方分析和GstD-GFP报告构建体。某些基因仅在一部分条件下发生改变,例如,响应过氧化氢的许多发育途径和信号传导基因的上调。虽然衰老与每种应激都有共同的特征,但衰老与氧化应激(高氧、过氧化氢、电离辐射)相关的应激比热应激更相似。衰老与许多线粒体基因的下调有关,包括电子传递链(ETC)基因和线粒体代谢基因,并且在过氧化氢应激和电离辐射应激时也观察到这些变化的子集。衰老与高氧共享最多的基因表达变化。线粒体和ETC基因在衰老过程中的广泛下调与线粒体维护中的衰老相关失败是一致的,这可能是衰老过程中观察到的氧化应激样和蛋白毒性应激样反应的基础。
Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.