Tengan Célia H, Kiyomoto Beatriz H, Godinho Rosely O, Gamba Juliana, Neves Afonso C, Schmidt Beny, Oliveira Acary S B, Gabbai Alberto A
Department of Neurology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):771-7. doi: 10.1016/j.bbrc.2007.05.184. Epub 2007 Jun 4.
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.
一氧化氮（NO）已被指出是线粒体呼吸控制中的一个重要因素，特别是由于其对细胞色素c氧化酶（COX）的抑制作用。然而，这种控制所涉及的所有事件仍未完全阐明。我们在患有线粒体疾病患者的肌肉活检中证明了一氧化氮合酶（NOS）活性存在区域化异常。在COX缺乏的纤维中，肌浆区的NOS活性降低，而在具有线粒体增殖的纤维的肌膜中发现活性增加。我们观察到患者中神经元型NOS（nNOS）表达增加，并且nNOS表达与线粒体含量之间存在相关性。用NO供体处理骨骼肌培养物会导致线粒体含量增加。我们的结果表明NO在具有线粒体缺陷的肌纤维的代偿机制中具有特定作用，并提示nNOS参与人类骨骼肌线粒体增殖的信号传导过程。
