Bamford Jeremy A, Lopaschuk Gary D, MacLean Ian M, Reinhart Marcia L, Dixon Walter T, Putman Charles T
Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Canada.
Can J Physiol Pharmacol. 2003 Nov;81(11):1072-82. doi: 10.1139/y03-110.
The present study examined the effects of chronic activation of 5'-AMP-activated protein kinase (AMPK) on the oxidative capacity and myosin heavy chain (MHC) based fibre phenotype of rodent fast- and slow-twitch muscles. Sprague-Dawley rats received daily injections for 4 weeks of the known AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or vehicle (control). The AICAR group displayed increases in hexokinase-II (HXK-II) activity, expression, and phosphorylation in fast-twitch muscles (P<0.001) but not in the slow-twitch soleus (SOL). In the AICAR group, citrate synthase (EC 4.1.3.7) and 3-hydroxyacyl-CoA-dehydrogenase (EC 1.1.1.35) were elevated 1.6- and 2.1-fold (P<0.05), respectively, in fast-twitch medial gastrocnemius (MG), and by 1.2- and 1.4-fold (P<0.05) in the slower-twitch plantaris (PLANT). No changes were observed in the slow-twitch SOL. In contrast, the activity of glyceraldehyde phosphate dehydrogenase (EC 1.2.1.12) remained unchanged in all muscles. AICAR treatment did not alter the MHC-based fibre type composition in fast- or slow-twitch muscles, as determined by immunohistochemical and electrophoretic analytical methods or by RT-PCR. We conclude that chronic activation of AMPK mimics the metabolic changes associated with chronic exercise training (increased oxidative capacity) in the fast-twitch MG and PLANT, but does not coordinately alter MHC isoform content or mRNA expression.
本研究检测了5'-AMP激活蛋白激酶（AMPK）长期激活对啮齿动物快、慢肌氧化能力和基于肌球蛋白重链（MHC）的纤维类型的影响。将已知的AMPK激活剂5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）或赋形剂（对照）每日注射给Sprague-Dawley大鼠，持续4周。AICAR组快肌中己糖激酶-II（HXK-II）活性、表达和磷酸化水平升高（P<0.001），而慢肌比目鱼肌（SOL）中无变化。在AICAR组中，快肌内侧腓肠肌（MG）中柠檬酸合酶（EC 4.1.3.7）和3-羟基酰基辅酶A脱氢酶（EC 1.1.1.35）分别升高1.6倍和2.1倍（P<0.05），慢肌比目鱼肌（PLANT）中分别升高1.2倍和1.4倍（P<0.05）。慢肌比目鱼肌中未观察到变化。相比之下，所有肌肉中磷酸甘油醛脱氢酶（EC 1.2.1.12）的活性均保持不变。通过免疫组织化学、电泳分析方法或RT-PCR测定，AICAR处理未改变快、慢肌中基于MHC的纤维类型组成。我们得出结论，AMPK的长期激活模拟了与长期运动训练相关的代谢变化（氧化能力增加），在快肌MG和PLANT中，但没有协同改变MHC同工型含量或mRNA表达。
