title: The role of nitric oxide in muscle fibers with oxidative phosphorylation defects.
abstract: NO has been pointed as an important player in the control of mitochondrial respiration, especially because of its inhibitory effect on cytochrome c oxidase (COX). However, all the events involved in this control are still not completely elucidated. We demonstrate compartmentalized abnormalities on nitric oxide synthase (NOS) activity on muscle biopsies of patients with mitochondrial diseases. NOS activity was reduced in the sarcoplasmic compartment in COX deficient fibers, whereas increased activity was found in the sarcolemma of fibers with mitochondrial proliferation. We observed increased expression of neuronal NOS (nNOS) in patients and a correlation between nNOS expression and mitochondrial content. Treatment of skeletal muscle culture with an NO donor induced an increase in mitochondrial content. Our results indicate specific roles of NO in compensatory mechanisms of muscle fibers with mitochondrial deficiency and suggest the participation of nNOS in the signaling process of mitochondrial proliferation in human skeletal muscle.
authors.affiliation: Department of Neurology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil. chtengan@neuro.epm.br
authors.forename: Célia H
authors.initials: CH
authors.lastname: Tengan
authors.forename: Beatriz H
authors.initials: BH
authors.lastname: Kiyomoto
authors.forename: Rosely O
authors.initials: RO
authors.lastname: Godinho
authors.forename: Juliana
authors.initials: J
authors.lastname: Gamba
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Neves
authors.forename: Beny
authors.initials: B
authors.lastname: Schmidt
authors.forename: Acary S B
authors.initials: AS
authors.lastname: Oliveira
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gabbai
mesh_terms: D000818:Animals; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010085:Oxidative Phosphorylation; D051381:Rats; D046509:Tissue Culture Techniques
chemical_list: D004272:DNA, Mitochondrial; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase