Increased p66Shc in the inner ear of D-galactose-induced aging mice with accumulation of mitochondrial DNA 3873-bp deletion: p66Shc and mtDNA damage in the inner ear during aging.
Increased p66Shc in the inner ear of D-galactose-induced aging mice with accumulation of mitochondrial DNA 3873-bp deletion: p66Shc and mtDNA damage in the inner ear during aging.
复制标题
D-半乳糖诱导的衰老小鼠内耳中 p66Shc 增加，线粒体 DNA 3873-bp 缺失积累：衰老过程中内耳中的 p66Shc 和 mtDNA 损伤。
DOI：
10.1371/journal.pone.0050483
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kong WJ
中科院分区：
文献类型：
--
作者：
Wu L;Sun Y;Hu YJ;Yang Y;Yao LL;Zhou XX;Wang H;Zhang R;Huang X;Kong WJ
衰老与线粒体DNA损伤有关。P66 Shc是一种与年龄相关的衔接蛋白，通过调节细胞对氧化应激的反应对线粒体代谢产生重大影响。本研究旨在建立D-半乳糖（D-gal）诱导的小鼠内耳衰老模型，并利用该模型探讨p66 Shc及其丝氨酸36位磷酸化形式在内耳衰老过程中的潜在作用。实时荧光定量PCR检测耳蜗外侧壁线粒体DNA 3873 bp缺失和p66 Shc mRNA表达水平。Western blot分析耳蜗外侧壁p66 Shc总蛋白、线粒体蛋白和Ser 36-P-p66 Shc蛋白的表达。免疫荧光法检测耳蜗外侧壁Ser 36-P-p66 Shc的表达定位。结果表明，与对照组相比，D-半乳糖处理组耳蜗外侧壁线粒体DNA 3873 bp缺失、p66 Shc总蛋白和线粒体蛋白水平以及Ser 36-P-p66 Shc水平均显著增加，Ser 36-P-p66 Shc主要定位于血管纹细胞的胞浆中。在衰老过程中，氧化应激相关的p66 Shc和Ser 36-P-p66 Shc的增加可能与内耳mtDNA 3873-bp缺失的积累有关。
Aging has been associated with mitochondrial DNA damage. P66Shc is an age-related adaptor protein that has a substantial impact on mitochondrial metabolism through regulation of the cellular response to oxidative stress. Our study aimed to establish a D-galactose (D-gal)-induced inner ear aging mouse model and to investigate the potential role of p66Shc and its serine 36-phosphorylated form in the inner ear during aging by using this model. Real-time PCR was performed to detect the mtDNA 3873-bp deletion and the level of p66Shc mRNA in the cochlear lateral wall. Western blot analysis was performed to analyze the total and mitochondrial protein levels of p66Shc and the level of Ser36-P-p66Shc in the cochlear lateral wall. Immunofluoresence was performed to detect the location of the Ser36-P-p66Shc expression in the cochlear lateral wall. The results showed that the accumulation of the mtDNA 3873-bp deletion, total and mitochondrial protein levels of p66Shc and level of Ser36-P-p66Shc were significantly increased in the cochlear lateral wall of the D-gal-treated group when compared to the control group and that Ser36-P-p66Shc was mainly localized in the cytoplasm of the cells in the stria vascularis. During aging, the oxidative stress-related increase of p66Shc and Ser36-P-p66Shc might be associated with the accumulation of the mtDNA 3873-bp deletion in the inner ear.
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影响因子：
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