Mitochondrial Electron Transport Complex I Is a Potential Source of Oxygen Free Radicals in the Failing Myocardium

• Published in: Circulation research 1999-08, Vol.85 (4), p.357-363
• Main Authors: Ide, Tomomi, Tsutsui, Hiroyuki, Kinugawa, Shintaro, Utsumi, Hideo, Kang, Dongchon, Hattori, Nobutaka, Uchida, Koji, Arimura, Ken-ichi, Egashira, Kensuke, Takeshita, Akira
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Dogs; Electron Transport; Electron Transport Complex I; Free Radicals - metabolism; Heart; Heart Failure - metabolism; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Medical sciences; Mitochondria, Heart - metabolism; NADH, NADPH Oxidoreductases - metabolism; Oxidative Stress; Reactive Oxygen Species - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.85.4.357

Oxidative stress in the myocardium may play an important role in the pathogenesis of congestive heart failure (HF). However, the cellular sources and mechanisms for the enhanced generation of reactive oxygen species (ROS) in the failing myocardium remain unknown. The amount of thiobarbituric acid reactive substances increased in the canine HF hearts subjected to rapid ventricular pacing for 4 weeks, and immunohistochemical staining of 4-hydroxy-2-nonenal ROS-induced lipid peroxides was detected in cardiac myocytes but not in interstitial cells of HF animals. The generation of superoxide anion was directly assessed in the submitochondrial fractions by use of electron spin resonance spectroscopy with spin trapping agent, 5,5′-dimethyl-1-pyrroline-N-oxide, in the presence of NADH and succinate as a substrate for NADH-ubiquinone oxidoreductase (complex I) and succinate-ubiquinone oxidoreductase (complex II), respectively. Superoxide production was increased 2.8-fold (P