Norrbom Jessica, Sundberg Carl Johan, Ameln Helene, Kraus William E, Jansson Eva, Gustafsson Thomas
Department of Physiology and Pharmacology, Section of Molecular Exercise Physiology, Karolinska Institutet, 171 77 Stockholm, Sweden.
J Appl Physiol (1985). 2004 Jan;96(1):189-94. doi: 10.1152/japplphysiol.00765.2003. Epub 2003 Sep 12.
Endurance training leads to many adaptational changes in several tissues. In skeletal muscle, fatty acid usage is enhanced and mitochondrial content is increased. The exact molecular mechanisms regulating these functional and structural changes remain to be elucidated. Contractile activity-induced metabolic perturbation has repeatedly been shown to be important for the induction of mitochondrial biogenesis. Recent reports suggest that the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha)/mitochondrial transcription factor A (Tfam) pathway is involved in exercise-induced mitochondrial biogenesis. In the present study, nine healthy men performed two 45-min bouts of one-legged knee extension exercise: one bout with restricted blood flow, and the other with nonrestricted blood flow to the working muscle. Muscle biopsies were obtained from the vastus lateralis muscle before exercise and at 0, 30, 120, and 360 min after the exercise bout. Biopsies were analyzed for whole muscle, as well as fiber-type specific mRNA expression of myocyte-enriched calcineurin interacting protein (MCIP)-1, PGC-1alpha, and downstream mitochondrial transcription factors. A novel finding was that, in human skeletal muscle, PGC-1alpha mRNA increased more after exercise with restricted blood flow than in the nonrestricted condition. No changes were observed for the mRNA of NRF-1, Tfam, mitochondrial transcription factor B1, and mitochondrial transcription factor B2. Muscle fiber type I and type II did not differ in the basal PGC-1alpha mRNA levels or in the expression increase after ischemic training. Another novel finding was that there was no difference between the restricted and nonrestricted exercise conditions in the increase of MCIP-1 mRNA, a marker for calcineurin activation. This suggests that calcineurin may be activated by exercise in humans and does not exclude that calcineurin could play a role in PGC-1 transcription activation in human skeletal muscle.
耐力训练会导致多个组织发生许多适应性变化。在骨骼肌中，脂肪酸的利用得到增强，线粒体含量增加。调节这些功能和结构变化的确切分子机制仍有待阐明。收缩活动诱导的代谢扰动已反复被证明对线粒体生物发生的诱导很重要。最近的报告表明，过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）/线粒体转录因子A（Tfam）途径参与运动诱导的线粒体生物发生。在本研究中，九名健康男性进行了两次45分钟的单腿伸膝运动：一次运动时工作肌肉的血流受限，另一次运动时工作肌肉的血流不受限。在运动前以及运动 bout 后的0、30、120和360分钟，从股外侧肌获取肌肉活检样本。对活检样本进行全肌肉分析，以及对富含肌细胞的钙调神经磷酸酶相互作用蛋白（MCIP）-1、PGC-1α和下游线粒体转录因子进行纤维类型特异性mRNA表达分析。一个新发现是，在人类骨骼肌中，血流受限运动后PGC-1α mRNA的增加比血流不受限情况下更多。未观察到NRF-1、Tfam、线粒体转录因子B1和线粒体转录因子B2的mRNA有变化。I型和II型肌纤维在基础PGC-1α mRNA水平或缺血训练后的表达增加方面没有差异。另一个新发现是，MCIP-1 mRNA（钙调神经磷酸酶激活的标志物）的增加在血流受限和不受限运动条件之间没有差异。这表明钙调神经磷酸酶可能在人类中被运动激活，并且不排除钙调神经磷酸酶可能在人类骨骼肌的PGC-1转录激活中发挥作用。
