Kitaoka Yu, Watanabe Daiki, Nonaka Yudai, Yagishita Kazuyoshi, Kano Yutaka, Hoshino Daisuke
Department of Human Sciences, Kanagawa University, Yokohama, Japan.
Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, Japan.
Physiol Rep. 2019 Oct;7(19):e14266. doi: 10.14814/phy2.14266.
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.
克伦特罗可诱导骨骼肌纤维类型由慢肌向快肌转变。这种肌纤维转变会降低线粒体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改变有关。为验证这一假设，我们研究了克伦特罗是否会改变大鼠骨骼肌的线粒体形态和线粒体调节蛋白。通过饮用水（30毫克/升）给大鼠施用克伦特罗3周。评估了胫骨前肌深层和浅层区域的肌球蛋白重链（MHC）亚型组成、线粒体形态以及融合和裂变调节蛋白水平。克伦特罗在胫骨前肌的两个区域均诱导了纤维类型从慢肌向快肌的转变。施用克伦特罗后，深层和浅层肌肉中视神经萎缩蛋白1、线粒体融合蛋白2和线粒体裂变蛋白1的水平显著降低（P<0.01），但动力相关蛋白1的水平未显著降低。此外，透射电子显微镜观察显示线粒体体积减小（P<0.05），横跨Z线的连续或相互作用线粒体比例增加（P<0.05）。我们发现，施用克伦特罗会诱导肌纤维类型组成向快肌表型转变，并导致线粒体形态改变，同时线粒体融合和裂变调节蛋白水平降低。这些线粒体形态改变可能会影响对骨骼肌代谢的有害作用。
