Role of calcineurin in exercise-induced mitochondrial biogenesis
Role of calcineurin in exercise-induced mitochondrial biogenesis
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DOI：
10.1152/ajpendo.00633.2005
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发表时间：
2006-06-01
影响因子：
5.1
通讯作者：
Holloszy, John O.
中科院分区：
文献类型：
--
作者：
Garcia-Roves, Pablo M.;Huss, Janice;Holloszy, John O.
提高胞质Ca 2+诱导肌管线粒体生物合成增加。这种现象模拟了骨骼肌对运动的适应性反应。据推测，在运动神经活动过程中，胞浆Ca2+的增加通过激活钙调神经磷酸酶刺激线粒体生物合成。组成型活性钙调神经磷酸酶的过表达增加了过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α）的表达，并诱导了参与肌细胞线粒体能量代谢的基因。本研究的目的是确定钙调神经磷酸酶是否在运动刺激线粒体生物合成中发挥作用。大鼠通过游泳连续运动5天。用环孢菌素抑制钙调磷酸酶并不能阻止运动诱导的PGC-1 α和一系列线粒体蛋白的增加。与其他线粒体蛋白相比，细胞色素氧化酶（考克斯）-I和-IV蛋白的增加被环孢菌素治疗阻断。环孢菌素的这种抑制作用发生在转录后水平上，环孢菌素-孔蛋白处理的大鼠运动后COX-Ⅰ和考克斯-IV mRNA的正常增加证明了这一点。环孢菌素的这种毒性作用可能是环孢菌素治疗导致肌肉呼吸能力下降的原因。总之，钙调磷酸酶的抑制并不能阻止运动诱导的骨骼肌线粒体生物合成的增加，这提供了钙调磷酸酶激活不介导适应性反应的证据。
Raising cytosolic Ca2+ induces an increase in mitochondrial biogenesis in myotubes. This phenomenon mimics the adaptive responses of skeletal muscle to exercise. It has been hypothesized that increases in cytosolic Ca2+ during motor nerve activity stimulate mitochondrial biogenesis by activating calcineurin. Overexpression of constitutively active calcineurin increases expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha ( PGC-1 alpha) and induction of genes involved in mitochondrial energy metabolism in muscle cells. The purpose of this study was to determine whether calcineurin plays a role in the stimulation of mitochondrial biogenesis by exercise. Rats were exercised on 5 successive days by means of swimming. Inhibition of calcineurin with cyclosporin did not prevent the exercise-induced increases in PGC-1 alpha and a range of mitochondrial proteins. In contrast to the other mitochondrial proteins, the increases in cytochrome oxidase ( COX)- I and - IV proteins were blocked by cyclosporin treatment. This inhibitory effect of cyclosporin occurred at the posttranscriptional level, as evidenced by normal increases in COX-I and COX- IV mRNAs in response to exercise in the cyclos-porin-treated rats. This toxic effect of cyclosporin may account for the decrease in muscle respiratory capacity reported to occur with cyclosporin treatment. In conclusion, inhibition of calcineurin does not prevent the exercise-induced increase in mitochondrial biogenesis in skeletal muscles, providing evidence that the adaptive response is not mediated by activation of calcineurin.