angiotensin ii-induced mitochondrial nox4 is a major endogenous source of oxidative stress in kidney tubular cells血管紧张素ii-induced线粒体nox4是一个主要的内源性肾小管细胞氧化应激的来源.pdfVIP

Angiotensin II-Induced Mitochondrial Nox4 Is a Major Endogenous Source of Oxidative Stress in Kidney Tubular Cells 1 1 2 1 2 2 Su-Mi Kim , Yang-Gyun Kim , Kyung-Hwan Jeong , Sang-Ho Lee , Tae-Won Lee , Chun-Gyoo Ihm , Ju- Young Moon1* 1 Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea, 2 Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Korea Abstract Angiotensin II (Ang II)-induced activation of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase leads to increased production of reactive oxygen species (ROS), an important intracellular second messenger in renal disease. Recent findings suggest that Ang II induces mitochondrial depolarization and further amplifies mitochondrial generation of ROS. We examined the hypothesis that ROS injury mediated by Ang II-induced mitochondrial Nox4 plays a pivotal role in mitochondrial dysfunction in tubular cells and is related to cell survival. In addition, we assessed whether angiotensin (1-7) peptide (Ang-(1-7)) was able to counteract Ang II-induced ROS-mediated cellular injury. Cultured NRK-52E cells were stimulated with 1026 M Ang II for 24 h with or without Ang-(1-7) or apocynin. Ang II simulated mitochondrial Nox4 and resulted in the abrupt production of mitochondrial superoxide (O 2) and hydrogen peroxide (H O ). Ang II also induced 2 2 2 depolarization of the mitochondrial membrane potential, and cytosolic secretion of cytochrome C and apoptosis-inducing factor (AIF)