Mitochondrial angiotensin receptors and aging.
Mitochondrial angiotensin receptors and aging.
复制标题
线粒体血管紧张素受体与衰老。
DOI：
10.1161/res.0b013e31823f05e0
复制
发表时间：
2011
影响因子：
20.1
通讯作者：
Inagami,Tadashi
中科院分区：
文献类型：
--
作者：
Inagami,Tadashi
The studies by Abadir et al. 1 connect the discovery of intra-mitochondrial presence of Ang II type 2 receptor AT2, to aging mtNOS. It is likely that increased NO in mitochondria would suppress O2 consumption and presumably ROS generation as summarized in Figure. The discovery of intra mitochondrial AT1 and AT2 and age-dependent changes in their levels provides new insights into the mechanisms that contribute to senescence. AT1 disrupted mice exhibited a 36% prolongation of life span associated with an increase in the number of mitochondria and upregulation of prosurvival genes for nicotinamide phosphoribosyl transferase and sirtuin 3 in the kidney. In cultured tubular epithelial cells Ang II downregulated sirtuin 3 mRNA, which was reversed by AT1 antagonist. 2 Resveratrol, a polyphenol found in red wine, is known to activate sirtuin 1, a longevity gene and suppresses AT1 in vascular smooth muscle cells. The AT1 suppression is considered to contribute to the longevity of vascular smooth muscle cells. Given the preservation of high mitochondrial level of AT2 by AT1 blocker, it raises the important question whether high mitochondrial AT2 or suppression of AT1 level is causally related longevity.The mechanisms by which the components of RAS, which are expressed from genomic DNA outside the mitochondria, are transported into inner mitochondria remain unknown. Mitochondria are known to contain NOS (mtNOS) in the inner membrane, which generates NO constitutively when the mitochondria are energized by succinate. The basal NOS activity is maintained by endogenous Ca2+ in the mitochondria. Increased mitochondrial Ca2+ levels markedly elevate NOS activity. 14 The findings by Abadir et al. also implicate intra mitochondrial Ang II as a regulator of NOS and mitochondrial function.
