Production of Reactive Oxygen Species in the Diabetic Heart:– Roles of Mitochondria and NADPH Oxidase –

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Author(s)

    • Nishio Satoru
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Saito Shotaro
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Kondo Hidekazu
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Fukui Akira
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Aoki Kouhei
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Yufu Kunio
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University
    • Nakagawa Mikiko
    • Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University

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<sup>+</sup>-H<sup>+</sup> exchanger and subsequent activation of Ca<sup>2+</sup>/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.  (<i>Circ J</i> 2014; <b>78:</b> 300–306)<br>

Journal

  • Circulation Journal

    Circulation Journal 78(2), 300-306, 2014

    The Japanese Circulation Society

Codes

  • NII Article ID (NAID)
    130003382238
  • Text Lang
    ENG
  • ISSN
    1346-9843
  • NDL Article ID
    025162356
  • NDL Call No.
    Z54-B860
  • Data Source
    NDL  J-STAGE 
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