Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy

Brenman, Jay E.; Chao, Daniel S.; Xia, Houhui; Aldape, Kenneth; Bredt, David S.

doi:10.1016/0092-8674(95)90471-9

Cited by 895 publications

(811 citation statements)

References 52 publications

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“…It has been shown that NO inhibits energy-generating pathways and decreases ATP levels in synaptosomes [17]. It is noteworthy that mistargeting of NO synthase from the sarcolemma to the cytoskeleton may be involved in pathological states such as muscle dystrophy [18]. In such conditions, NO may exert inhibition of key enzymes at unwanted sites.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of creatine kinase by S‐nitrosoglutathione

1996

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The sarcoplasmic reticulum-bound creatine kinase from rabbit skeletal muscle was inhibited by the nitric oxide donor S-nitrosoglutathione (GSNO). This led to a decrease in Ca 2÷ uptake in sarcoplasmic reticulum vesicles when the transport was driven by ATP generated from phosphocreatine and ADP. In contrast, the Ca 2÷ transport measured using 2 mM ATP as substrate was unaffected by GSNO up to 200 IxlVl. GSNO (5--20 lEVI) inhibited the activity of both soluble and membrane-bound creatine kinase. Oxyhemoglobin (15-40 lEVI) protected creatine kinase against inactivation by GSNO. The inhibition by 10 ~M GSNO was reversed by the addition of dithiothreitol (2 raM). The results indicate that nitric oxide (NO, including NO +, NO and NO-) inactivates creatine kinase in vitro by promoting nitrosylation of critical sulphydryl groups of the enzyme.

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Section: Discussionmentioning

confidence: 99%

Inhibition of creatine kinase by S‐nitrosoglutathione

1996

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“…NO has shown to regulate cytoskeletal proteins,116 and nNOS isoform, strongly expressed in glycolytic muscle fibres,117 has been reported as the prime source of NO release from skeletal muscle 118. The importance of NO signalling in muscle physiology is highlighted in mdx mice119 and humans with Duchenne muscular dystrophy 112, 120. NO responses are largely mediated via cysteine (Cys) S ‐nitrosylation or by coordinated interactions with heme or non‐heme Fe and Cu 121…”

Section: Chemistry Of Reactive Oxygen and Nitrogen Species Produced Bmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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“…Skeletal muscles express two alternatively spliced nNOS isoforms, nNOSμ and nNOSβ, both of which are expressed in fast and slow muscle types (Silvagno et al 1996;Stamler and Meissner 2001;Percival et al 2010, Figure 1). nNOSμ is scaffolded to the subsarcolemmal dystrophin glycoprotein complex (DGC) and neuromuscular junction (Brenman et al 1995(Brenman et al , 1996Adams et al 2000). The sarcolemmal nNOSμ association requires α-syntrophin, dystrophin, and α-dystrobrevin (Brenman et al 1995(Brenman et al , 1996Grady et al 2000;Adams et al 2000Adams et al , 2008.…”

Section: Introductionmentioning

confidence: 99%

nNOS regulation of skeletal muscle fatigue and exercise performance

Percival

2011

Biophys Rev

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Neuronal nitric oxide synthases (nNOS) are Ca 2+ /calmodulin-activated enzymes that synthesize the gaseous messenger nitric oxide (NO). nNOSμ and the recently described nNOSβ, both spliced nNOS isoforms, are important enzymatic sources of NO in skeletal muscle, a tissue long considered to be a paradigmatic system for studying NO-dependent redox signaling. nNOS is indispensable for skeletal muscle integrity and contractile performance, and deregulation of nNOSμ signaling is a common pathogenic feature of many neuromuscular diseases. Recent evidence suggests that both nNOSμ and nNOSβ regulate skeletal muscle size, strength, and fatigue resistance, making them important players in exercise performance. nNOSμ acts as an activity sensor and appears to assist skeletal muscle adaptation to new functional demands, particularly those of endurance exercise. Prolonged inactivity leads to nNOS-mediated muscle atrophy through a FoxO-dependent pathway. nNOS also plays a role in modulating exercise performance in neuromuscular disease. In the mdx mouse model of Duchenne muscular dystrophy, defective nNOS signaling is thought to restrict contractile capacity of working muscle in two ways: loss of sarcolemmal nNOSμ causes excessive ischemic damage while residual cytosolic nNOSμ contributes to hypernitrosylation of the ryanodine receptor, causing pathogenic Ca 2+ leak. This defect in Ca 2+ handling promotes muscle damage, weakness, and fatigue. This review addresses these recent advances in the understanding of nNOS-dependent redox regulation of skeletal muscle function and exercise performance under physiological and neuromuscular disease conditions.

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Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy

Cited by 895 publications

References 52 publications

Inhibition of creatine kinase by S‐nitrosoglutathione

Inhibition of creatine kinase by S‐nitrosoglutathione

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

nNOS regulation of skeletal muscle fatigue and exercise performance

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