Altered expression of the adenine nucleotide translocase isoforms and decreased ATP synthase activity in skeletal muscle mitochondria in heart failure
Altered expression of the adenine nucleotide translocase isoforms and decreased ATP synthase activity in skeletal muscle mitochondria in heart failure
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DOI：
10.1016/j.yjmcc.2009.02.009
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发表时间：
2009-06-01
影响因子：
5
通讯作者：
Hoppel, Charles L.
中科院分区：
文献类型：
--
作者：
Rosca, Mariana G.;Okere, Isidore A.;Hoppel, Charles L.
运动不耐受是心力衰竭（HF）综合征的一个组成部分。我们的目的是确定骨骼肌线粒体的缺陷，这可能有助于周围性肌病的发展。从对照犬（N=5）和起搏诱导的HF犬（N =5）的腓肠肌中分离肌膜下（SSM）和原纤维间（IFM）线粒体。测量线粒体的综合功能（氧化磷酸化）和线粒体电子传递链（ETC）复合物的个体活动的补充与磷酸化装置的组件的量和活性的评估。从HF分离的骨骼肌线粒体的两个群体具有显著降低的ADP刺激的（状态3）呼吸速率与复合物1，11和III底物。骨骼肌SSM的呼吸频率的降低既不缓解后崩溃的线粒体电位与解偶联剂，也没有增加的最大ADP浓度的存在下，显示在ETC的缺陷，这需要进一步调查。与此相反，骨骼肌IFM从HF的呼吸率与解偶联剂缓解，并在最大ADP浓度的存在下部分改善。在这些IFM中，检测到磷酸化装置的改变，ANT亚型2的量减少，亚型1的量增加。IFM功能障碍可以通过ANT亚型的这种转变来解释。总之，起搏诱导的HF导致骨骼肌线粒体氧化磷酸化的减少，由于ETC和磷酸化装置的缺陷。(C)2009 Elsevier Inc. All rights reserved.
Exercise intolerance is a component of heart failure (HF) syndrome. We aimed to identify the defects in skeletal muscle mitochondria which may contribute to the development of peripheral myopathy. Subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria were isolated from gastrocnemius muscle of control dogs (N=5) and dogs with pacing-induced HF (N=5). The measurement of integrated mitochondrial function (oxidative phosphorylation) and of individual activities of mitochondrial electron transport chain (ETC) complexes was complemented with the assessment of the amount and activity of the components of the phosphorylation apparatus. Both populations of skeletal muscle mitochondria isolated from HF have significantly decreased ADP-stimulated (state 3) respiratory rates with complex 1, 11 and III substrates. The decrease in respiratory rates of skeletal muscle SSM are neither relieved upon collapsing the mitochondrial potential with an uncoupler nor increased in the presence of maximal ADP concentrations showing a defect in the ETC, which needs further investigation. In contrast, respiratory rates of skeletal muscle IFM from HF were relieved with the uncoupler and partially improved in the presence of maximal ADP concentrations. In these IFM, alterations in the phosphorylation apparatus were detected with a decreased amount of ANT isoform 2 and increased amount of isoform 1. The IFM dysfunction may be explained by this shift in ANT isoforms. In conclusion, pacing-induced HF causes a decrease in the oxidative phosphorylation of skeletal muscle mitochondria due to defects in the ETC and phosphorylation apparatus. (C) 2009 Elsevier Inc. All rights reserved.