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具有遗传性低氧运动耐力差异的小鼠骨骼肌中的高能磷酸浓度和AMPK磷酸化

High energy phosphate concentrations and AMPK phosphorylation in skeletal muscle from mice with inherited differences in hypoxic exercise tolerance.

作者信息

Overton Jeffrey D, Adams Glenn S, McCall R Dale, Kinsey Stephen T

机构信息

Department of Biology and Marine Biology, University of North Carolina Wilmington, 601 South College Road, Wilmington, NC 28403-5915, USA.

出版信息

Comp Biochem Physiol A Mol Integr Physiol. 2009 Apr;152(4):478-85. doi: 10.1016/j.cbpa.2008.11.019. Epub 2008 Dec 6.

DOI:10.1016/j.cbpa.2008.11.019
PMID:19100334
Abstract

The effect of chronic hypobaric hypoxia (1/2 atmospheric pressure) on high energy phosphate (HEP) compounds was investigated in slow (soleus; SOL) and fast twitch (extensor digitorum longus; EDL) muscle from 3 strains of mice with large differences in hypoxic exercise tolerance (HET). Phosphocreatine concentration ([PCr]) decreased 16-29% following hypoxia in EDL and SOL in all strains, while [ADP] and [AMP] increased. In the EDL, HET was negatively correlated with the PCr/ATP ratio and positively correlated with the ATP/P(i) ratio. The free energy of ATP hydrolysis (DeltaG(obs)) remained constant despite the substantial changes that occurred in HEP profiles. The alteration of HEP set points and preservation of DeltaG(obs) are consistent with the notion that (1) maximal rates of steady-state ATP turnover are reduced under hypoxia, and (2) HEP perturbations during rest to work transitions are reduced in skeletal muscle from hypoxia acclimated animals. We therefore expected a lower phosphorylation ratio of AMP-activated protein kinase (AMPK-P/AMPK) during stimulation in hypoxic acclimated animals. However, neither the resting nor stimulated AMPK-P/AMPK was influenced by hypoxia, although there were significant differences among strains.

摘要

研究了慢性低压缺氧(1/2大气压)对3种低氧运动耐力(HET)差异很大的小鼠品系的慢肌(比目鱼肌;SOL)和快肌(趾长伸肌;EDL)中高能磷酸(HEP)化合物的影响。在所有品系的EDL和SOL中,缺氧后磷酸肌酸浓度([PCr])下降了16%-29%,而[ADP]和[AMP]增加。在EDL中,HET与PCr/ATP比值呈负相关,与ATP/P(i)比值呈正相关。尽管HEP谱发生了显著变化,但ATP水解的自由能(ΔG(obs))保持恒定。HEP设定点的改变和ΔG(obs)的保持与以下观点一致:(1)在缺氧条件下,稳态ATP周转的最大速率降低;(2)在从低氧适应动物的骨骼肌中,从休息到工作转变期间的HEP扰动减少。因此,我们预计在低氧适应动物受到刺激时,AMP激活蛋白激酶(AMPK-P/AMPK)的磷酸化比率会降低。然而,尽管品系之间存在显著差异,但无论是静息还是受刺激状态下的AMPK-P/AMPK都不受缺氧影响。

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