title: Nitric oxide in skeletal muscle: role on mitochondrial biogenesis and function.
abstract: Nitric oxide (NO) has been implicated in several cellular processes as a signaling molecule and also as a source of reactive nitrogen species (RNS). NO is produced by three isoenzymes called nitric oxide synthases (NOS), all present in skeletal muscle. While neuronal NOS (nNOS) and endothelial NOS (eNOS) are isoforms constitutively expressed, inducible NOS (iNOS) is mainly expressed during inflammatory responses. Recent studies have demonstrated that NO is also involved in the mitochondrial biogenesis pathway, having PGC-1α as the main signaling molecule. Increased NO synthesis has been demonstrated in the sarcolemma of skeletal muscle fiber and NO can also reversibly inhibit cytochrome c oxidase (Complex IV of the respiratory chain). Investigation on cultured skeletal myotubes treated with NO donors, NO precursors or NOS inhibitors have also showed a bimodal effect of NO that depends on the concentration used. The present review will discuss the new insights on NO roles on mitochondrial biogenesis and function in skeletal muscle. We will also focus on potential therapeutic strategies based on NO precursors or analogs to treat patients with myopathies and mitochondrial deficiency.
authors.affiliation: Department of Neurology and Neurosurgery, Paulista School of Medicine, Federal University of São Paulo, Sao Paulo 04039-032, Brazil. chtengan@unifesp.br.
authors.forename: Celia Harumi
authors.initials: CH
authors.lastname: Tengan
authors.forename: Gabriela Silva
authors.initials: GS
authors.lastname: Rodrigues
authors.forename: Rosely Oliveira
authors.initials: RO
authors.lastname: Godinho
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism*; D063269:Mitochondrial Turnover / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003576:Electron Transport Complex IV