Characterization of aquaporin-4 in muscle and muscular dystrophy
Characterization of aquaporin-4 in muscle and muscular dystrophy
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DOI：
10.1096/fj.01-0327com
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发表时间：
2002-07-01
期刊：
影响因子：
4.8
通讯作者：
Campbell, KP
中科院分区：
文献类型：
--
作者：
Crosbie, RH;Dovico, SA;Campbell, KP
水通道蛋白是一个不断增长的跨膜蛋白家族，它能跨细胞膜运输水，在某些情况下，还能运输甘油和尿素。水通道蛋白-4(Aquaporin-4，AQP4)在骨骼肌的肌膜中含量丰富，可能在调节收缩过程中细胞体积和静水压力的快速变化中发挥作用，以防止肌膜的损伤。最近的证据表明，AQP4在dystrophin缺陷的mdx小鼠中缺失，这表明AQP4与dystrophin相关，并在营养不良过程中发挥作用。为了研究水通道蛋白与肌肉疾病的关系，以及水通道蛋白和肌营养不良蛋白之间的关系，我们研究了水通道蛋白在各种肌营养不良和心肌病小鼠模型中的表达。我们发现，尽管没有dystrophin，AQP4在肾癌前病变的MDX肌肉中仍有表达，并且AQP4在肌肉退变开始后丢失。对不同的dystrophin转基因小鼠的分析表明，即使在dystrophin-糖蛋白复合体存在的情况下，AQP4也会丢失，这表明AQP4的丢失不是DGC丢失的直接原因。AQP4也在肌营养不良症中丢失，这些肌营养不良症是由肌聚糖基因的初级突变引起的。综上所述，我们的数据表明，骨骼肌中AQP4的缺失与肌营养不良有关，是发病机制的共同特征。
Aquaporins are a growing family of transmembrane proteins that transport water and, in some cases, glycerol and urea across cellular membranes. Aquaporin-4 (AQP4) is enriched at the sarcolemma of skeletal muscle and may play a role in accommodating the rapid changes in cell volume and hydrostatic forces that occur during contraction in order to prevent damage to the sarcolemma. Recent evidence has shown that AQP4 is absent in dystrophin-deficient mdx mice, suggesting that AQP4 associates with dystrophin and has a role in the dystrophic process. To examine the relationship between aquaporins and muscle disease, and between aquaporins and dystrophin, we have investigated aquaporin expression in various mouse models of muscular dystrophy and cardiomyopathy before and after the onset of pathology. We find that AQP4 is expressed in prenecrotic mdx muscle despite the absence of dystrophin and that AQP4 is lost after the onset of muscle degeneration. Analysis of various dystrophin transgenic mice reveals that AQP4 is lost even when the dystrophin-glycoprotein complex is present, suggesting that loss of AQP4 is not directly resulting from loss of the DGC. AQP4 was also lost in muscular dystrophies caused by primary mutations in the sarcoglycan genes. Taken together, our data demonstrate that AQP4 loss in skeletal muscle correlates with muscular dystrophy and is a common feature of pathogenesis.