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Role of AMP kinase and calcineurin for skeletal muscle histochemical and biochemical adaptations : skeletal muscle signal transduction by endurance training

AMP激酶和钙调神经磷酸酶在骨骼肌组织化学和生化适应中的作用：耐力训练的骨骼肌信号转导

基本信息

批准号：
16300209
负责人：
KUMAGAI Shuzo
金额：
$ 7.74万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300209/
关键词：
AMP kinase endurance training skeletal muscle PGC-1α calcineurin 持久的運動 GULT-4

项目摘要

AMP kinase (AMPK) was considered as one of the signal transduction factors with endurance training in skeletal muscle. The rats ran on treadmill and immediately soleus muscle was excised for determining AMPK phosphorylation. Then, AMPK phosphorylation was significantly increased as AMPK specific activator AICAR. The rats were trained such exercise for 14 days and then soleus muscle transcriptional coactivator PGC-1α, transcriptional factor PPARδ, and glucose transporter 4 protein expressions and oxidative enzyme activities such as CS, MDH, and βHAD were increased. These results would suggest that metabolic adaptations of skeletal muscle by endurance training are at least in part related to AMPK. In addition, AMPK activation might increase PGC-1α and PPARδ expression that enhances the oxidative enzyme activities. In the next, anti-diabetic drug metformin, which can activate AMPK, was administered to the rats for 14 days. Then, skeletal muscle PGC-1α protein expression was significantly increased. Furthermore, oxidative enzyme activities including CS and βHAD were increased by metformin treatment as AICAR. These results raise the possibility that metformin at least partially improves the diabetic conditions as the same mechanisms of the endurance exercise training. We also examine the role of calcineurin which is considered another signal transduction factors with endurance training in skeletal muscle. The rats were treated with calcineurin inhibitor and then skeletal muscle glycolytic enzyme activities were increased without any change of oxidative enzyme activities. The results may imply that calcineurin play a role for the decrease of glycolytic enzyme activities by endurance exercise training.

AMP激酶（AMPK）被认为是骨骼肌耐力训练的信号转导因子之一。大鼠在跑步机上跑步，并立即切除比目鱼肌用于测定AMPK磷酸化。AMPK特异性激活剂AICAR使AMPK磷酸化水平显著升高。运动14 d后，大鼠比目鱼肌转录辅激活因子PGC-1α、转录因子PPARδ和葡萄糖转运蛋白4蛋白表达增加，CS、MDH和βHAD等氧化酶活性升高。这些结果表明，骨骼肌耐力训练的代谢适应至少部分与AMPK有关。此外，AMPK的激活可能增加了PGC-1α和PPARδ的表达，从而增强了氧化酶的活性。接下来，将可激活AMPK的抗糖尿病药物二甲双胍给予大鼠14天。骨骼肌PGC-1α蛋白表达显著增加。此外，二甲双胍处理可增加氧化酶活性，包括CS和βHAD，如AICAR。这些结果提高了二甲双胍至少部分改善糖尿病状况的可能性，与耐力运动训练的机制相同。我们还研究了钙调神经磷酸酶，这被认为是另一个信号转导因子与骨骼肌耐力训练的作用。用钙调磷酸酶抑制剂处理后，大鼠骨骼肌糖酵解酶活性增加，而氧化酶活性无任何变化。结果提示，钙调神经磷酸酶在耐力运动训练降低糖酵解酶活性中起一定作用。