Effects of clenbuterol administration on mitochondrial morphology and its regulatory proteins in rat skeletal muscle
Effects of clenbuterol administration on mitochondrial morphology and its regulatory proteins in rat skeletal muscle
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DOI：
10.14814/phy2.14266
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发表时间：
2019-10-01
影响因子：
2.5
通讯作者：
Hoshino, Daisuke
中科院分区：
文献类型：
--
作者：
Kitaoka, Yu;Watanabe, Daiki;Hoshino, Daisuke
克伦特罗可诱导骨骼肌由慢变快的纤维型转变。这种肌肉纤维的转变降低了线粒体的氧化能力和呼吸功能。我们推测，克伦特罗介导的氧化能力降低与线粒体形态的改变有关。为了验证这一假设，我们研究了克伦特罗是否改变了大鼠骨骼肌中线粒体的形态和线粒体调节蛋白。给大鼠灌胃瘦肉精30 mg/L，连续3周。检测胫前肌深部和浅部肌球蛋白重链(MHC)亚型组成、线粒体形态、融合和分裂调节蛋白水平。克伦特罗在TA的两个区域均引起纤维类型由慢向快的转变。克伦特罗治疗后，深浅肌中视神经萎缩蛋白1、丝裂蛋白2和线粒体分裂蛋白1的表达水平显著降低(P<；0.01)，而动力蛋白相关蛋白1的表达水平无明显变化。同时，透射电子显微镜观察显示线粒体体积减小(P<；0.05)，跨Z线的连续或相互作用的线粒体比例增加(P<；0.05)。我们发现，克伦特罗的应用诱导了肌肉纤维类型组成向快速表型的转变，并导致线粒体形态的改变，伴随而来的是线粒体融合和分裂调节蛋白水平的降低。这些线粒体形态的改变可能会影响对骨骼肌代谢的有害影响。
Clenbuterol induces a slow-to-fast fiber type transition in skeletal muscle. This muscle fiber transition decreased mitochondrial oxidative capacity and respiratory function. We hypothesized that the clenbuterol-mediated reduction in oxidative capacity is associated with the alteration in mitochondrial morphology. To verify this hypothesis, we examined whether clenbuterol alters mitochondrial morphology and mitochondrial regulatory proteins in rat skeletal muscle. Clenbuterol was administered to rats via drinking water (30 mg/L) for 3 weeks. Myosin heavy chain (MHC) isoform composition, mitochondrial morphology, and fusion and fission regulatory protein levels in deep region and superficial region in tibialis anterior (TA) muscles were assessed. Clenbuterol induced the fiber type transition from slow to fast in both the regions of TA. The levels of optic atrophy protein 1, mitofusin 2, and mitochondrial fission 1, but not of dynamin-related protein 1, significantly decreased in deep and superficial muscles after clenbuterol administration (P < 0.01). Also, observation using the transmission electron microscopy showed a decrease in mitochondrial volume (P < 0.05) and an increase in proportion of continuous or interacting mitochondria across Z-lines (P < 0.05). We showed that clenbuterol administration induces a transition in the muscle fiber type composition toward fast phenotype and causes alterations in mitochondrial morphology with a concomitant decrease in mitochondrial fusion and fission regulatory protein levels. These mitochondrial morphological alterations may influence deleterious effects on skeletal muscle metabolism.