Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy
Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy
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DOI：
10.1073/pnas.93.17.9142
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发表时间：
1996-08-20
影响因子：
11.1
通讯作者：
Stull, JT
中科院分区：
文献类型：
--
作者：
Chang, WJ;Iannaccone, ST;Stull, JT
神经型一氧化氮合酶（nNOS）在快速收缩的骨骼肌纤维中主要呈颗粒状，而在大脑中具有更大的溶解性。免疫组化显示nNOS定位于肌膜，在力传递部位、肌腱连接处和脊柱处富集。由于这种分布与肌营养不良蛋白相似，我们确定nNOS的表达是否受到肌营养不良蛋白缺失的影响。Duchenne型肌营养不良患者骨骼肌组织中缺乏显著的nNOS免疫反应性和酶活性。同样，与C57中心小鼠相比，mdr小鼠骨骼肌中可溶性和颗粒性nNOS均显著降低，与肌营养不良蛋白结合蛋白α - 1-syntrophin mRNA水平相比，mdr肌肉中nNOS mRNA水平也显著降低，C57骨骼肌中nNOS水平在2 ~ 52周龄显著升高。这可能表明NO在衰老相关过程中的生理作用，生化纯化很容易将nNOS从肌营养不良蛋白-糖蛋白复合物中分离出来。因此，nNOS不是肌营养不良蛋白-糖蛋白复合物的组成部分，也不仅仅是另一种肌营养不良蛋白相关蛋白，因为nNOS mRNA和蛋白的表达都受到肌营养不良蛋白表达的影响。
Neuronal nitric oxide synthase (nNOS) in fast-twitch skeletal muscle fibers is primarily particulate in contrast to its greater solubility in brain, Immunohistochemistry shows nNOS localized to the sarcolemma, with enrichment at force transmitting sites, the myotendinous junctions, and costameres, Because this distribution is similar to dystrophin, we determined if nNOS expression was affected by the loss of dystrophin, Significant nNOS immunoreactivity and enzyme activity was absent in skeletal muscle tissues from patients with Duchenne muscular dystrophy, Similarly, in dystrophin-deficient skeletal muscles from mdr mice both soluble and particulate nNOS was greatly reduced compared with C57 central mice, nNOS mRNA was also reduced in mdr muscle in contrast to mRNA levels for a dystrophin binding protein, alpha 1-syntrophin, nNOS levels increased dramatically from 2 to 52 weeks of age in C57 skeletal muscle, which mag indicate a physiological role for NO in aging-related processes, Biochemical purification readily dissociates nNOS from the dystrophin-glycoprotein complex. Thus, nNOS is not an integral comp one nt of the dystrophin-glycoprotein complex and is not simply another dystrophin-associated protein since the expression of both nNOS mRNA and protein is affected by dystrophin expression.