Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm.
Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm.
复制标题
营养不良小鼠膈肌肌球蛋白重链表达和收缩功能的适应。
DOI：
10.1152/ajpcell.1993.265.3.c834
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Kelly,AM
中科院分区：
文献类型：
--
作者：
Petrof,BJ;Stedman,HH;Shrager,JB;Eby,J;Sweeney,HL;Kelly,AM
X染色体连锁的肌营养不良（mdx）小鼠缺乏肌膜下蛋白抗肌萎缩蛋白，因此代表了人类杜氏肌营养不良症的遗传同源物。本研究检查了年轻（3-4个月）和老年（22-24个月）对照组和mdx小鼠膈肌收缩特性和肌球蛋白重链（MHC）表达的变化。在年轻mdx小鼠中，最大等长张力（Po）降低至对照值的50%。共表达I型（慢）和IIa型MHC的纤维以及表达胚胎MHC的再生纤维增加，而IIx/B纤维减少。在旧mdx组中，Po进一步降低至对照组的25%，并且沿着明显增加的膈肌耐力，抽搐动力学减慢。这些变化与I型MHC纤维增加约7倍和IIx/B纤维群的实际消除有关;没有可检测到的胚胎MHC表达。我们得出结论，mdx隔膜响应于进行性肌肉退化，并转变为与功率输出减少和肌肉耐力增强相关的较慢表型。在进行性肌纤维破坏的情况下，这些变化可能有助于保持收缩功能，并通过减少细胞能量需求来促进剩余肌纤维的更大存活。
The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements.