title: Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase.
abstract: Reactive oxygen species (ROS) are the main facilitators of cardiovascular complications in diabetes mellitus (DM), and the ROS level is increased in cultured cells exposed to high glucose concentrations or in diabetic animal models. Emerging evidence shows that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production in the diabetic heart. Hyperpolarization of the mitochondrial inner membrane potentials and impaired mitochondrial function promote ROS production in the mitochondria of the diabetic heart. Uncoupling proteins are upregulated and may reduce the ROS level by depolarizing the mitochondrial inner membrane potential. NADPH oxidase is another major site of ROS production and its contribution to DM-induced ROS increase has been elucidated not only in vascular smooth muscle cells and endothelial cells, but also in cardiomyocytes. Protein kinase C, angiotensin II, and advanced glycation endproducts (AGEs)/receptor for AGEs can activate NADPH oxidase. Increased intracellular calcium level mediated via the Na(+)-H(+) exchanger and subsequent activation of Ca(2+)/calmodulin-dependent protein kinase II may also activate NADPH oxidase. This review presents the current understanding of the mechanisms of ROS production, focusing especially on the roles of mitochondria and NADPH oxidase.
authors: Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University.
authors: Yasushi
authors: Y
authors: Teshima
authors: Naohiko
authors: N
authors: Takahashi
authors: Satoru
authors: S
authors: Nishio
authors: Shotaro
authors: S
authors: Saito
authors: Hidekazu
authors: H
authors: Kondo
authors: Akira
authors: A
authors: Fukui
authors: Kouhei
authors: K
authors: Aoki
authors: Kunio
authors: K
authors: Yufu
authors: Mikiko
authors: M
authors: Nakagawa
authors: Tetsunori
authors: T
authors: Saikawa
mesh_terms: D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases