NADPH oxidase and cardiac failure.
Increases in oxidative stress in the heart play an important role in mediating hypertrophy, apoptosis, fibrosis, mitochondrial dysfunction, and the consequent development of heart failure. Although it has been widely believed that electron leakage from the mitochondrial electron transport chain is the primary source of oxidative stress in the failing heart, increasing lines of evidence suggest that enzymes which produce reactive oxygen species may also contribute to it. NADPH oxidases are transmembrane enzymes dedicated to producing superoxide (O(2)(-)) by transferring an electron from NAD(P)H to molecular oxygen. Nox4 is a major NADPH oxidase isoform expressed in the heart. Nox4 is localized primarily at mitochondria in cardiac myocytes, and upregulation of Nox4 hypertrophic stimuli enhances O(2)(-) production, apoptosis, and mitochondrial dysfunction, thereby playing an important role in mediating cardiac dysfunction. Since Nox4 could be a key molecule mediating oxidative stress and pathological hypertrophy, it may serve as an important target of heart failure treatment. In this review, the importance of NADPH oxidases as sources of increased oxidative stress in the failing heart and the role of Nox4 in mediating growth and death of cardiac myocytes are discussed.
Kuroda
Junya
J
Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, 185 S Orange Ave., MSB G609, Newark, NJ 07103, USA.
Sadoshima
Junichi
J
D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism; D006333:Heart Failure / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D015415:Biomarkers; D016877:Oxidants; D017382:Reactive Oxygen Species; D013481:Superoxides; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human