SIRT3
氧化应激
过氧化氢酶
血管紧张素II
线粒体
超氧化物歧化酶
线粒体DNA
肾素-血管紧张素系统
化学
氧化磷酸化
内分泌学
内科学
线粒体ROS
激活剂(遗传学)
活性氧
细胞生物学
生物
生物化学
NAD+激酶
酶
锡尔图因
医学
受体
基因
血压
作者
Li Yong,Genhai Shen,Chen Yu,Guangfei Li,Junkang Shen,Jie Gong,Youjia Xu
标识
DOI:10.1016/j.bbrc.2014.10.123
摘要
Previous report showed that angiotensin II accelerates osteoporosis, and recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. However, the underling mechanism by which angiotensin II induces bone dysfunction is largely unknown. Here in this study, we show that angiotensin II induces mitochondrial oxidative stress and mitochondrial DNA (mtDNA) damage. We find that the protein and RNA levels of mitochondrial catalase and manganese superoxide dismutase (MnSOD) are decreased in osteoblasts in the presence of angiotensin II. Further, we show that angiotensin II inhibits the protein level of SIRT1, but not SIRT3, which results in the hyperacetylation of the forkhead box O3a (FoxO3a) and inhibition of the expression of catalase and MnSOD. Finally, we show that SRT3025 (Sirt1 activator) and Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP, a MnSOD mimetics) can markedly reduce mitochondrial oxidative stress and mtDNA damage. In summary, we identify a novel SIRT1–FoxO3a–MnSOD axis in angiotensin II-induced mitochondrial oxidative stress and mtDNA damage in osteoblasts.
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