title: Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres.
abstract: Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events.
authors: Department of Neurology &Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo;São Paulo, Brazil.
authors: Gabriela Silva
authors: GS
authors: Rodrigues
authors: Division of Cellular Pharmacology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Rosely Oliveira
authors: RO
authors: Godinho
authors: Department of Neurology &Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo;São Paulo, Brazil.
authors: Beatriz Hitomi
authors: BH
authors: Kiyomoto
authors: Department of Neurology &Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo;São Paulo, Brazil.
authors: Juliana
authors: J
authors: Gamba
authors: Department of Neurology &Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo;São Paulo, Brazil.
authors: Acary Souza Bulle
authors: AS
authors: Oliveira
authors: Department of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Beny
authors: B
authors: Schmidt
authors: Department of Neurology &Neurosurgery, Escola Paulista de Medicina, Universidade Federal de São Paulo;São Paulo, Brazil.
authors: Célia Harumi
authors: CH
authors: Tengan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase