Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers.
Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers.
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与过氧化氢处理骨骼肌纤维相关的肌球蛋白的功能、结构和化学变化。
DOI：
10.1152/ajpcell.00232.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Thomas,DavidD
中科院分区：
文献类型：
--
作者：
Prochniewicz,Ewa;Lowe,DawnA;Spakowicz,DanielJ;Higgins,LeeAnn;O'Conor,Kate;Thompson,LaDoraV;Ferrington,DeborahA;Thomas,DavidD
为了了解氧化诱导的肌肉收缩性抑制的分子机制，我们研究了过氧化氢对渗透兔腰肌肌纤维的影响，重点研究了从这些纤维中纯化的肌球蛋白的变化。5毫米的过氧化氧化降低了纤维的收缩性（等距力和缩短速度），但没有显著改变肌原纤维和分离肌球蛋白的酶活性。用二硫苏糖醇处理纤维后，抑制作用被逆转。50 mM的过氧化氧化对纤维的收缩性有更明显和不可逆的抑制作用，也影响肌原纤维、肌球蛋白和肌动球蛋白的酶活性。过氧化处理也影响了收缩性的调节，导致纤维在缺乏钙的情况下活化。肌肉纤维中自旋标记肌球蛋白的电子顺磁共振显示，氧化在放松条件下（低钙）增加了处于强结合结构状态的肌球蛋白头的比例，而在激活条件下（高钙）没有影响。肌球蛋白结构状态分布的这种变化为观察到的收缩和调节功能的变化提供了合理的解释。质谱分析表明，50 mM而不是5 mM的过氧化氢通过靶向多个甲硫氨酸残基，诱导了肌球蛋白亚片段1基本轻链和重链的两种同工型的氧化修饰。我们得出结论：1)通过氧化肌球蛋白来抑制肌纤维收缩性发生在高而不是低浓度的过氧化物中；2)氧化的抑制作用表明蛋氨酸在肌球蛋白功能中起着关键的、以前未知的作用。
To understand the molecular mechanism of oxidation-induced inhibition of muscle contractility, we have studied the effects of hydrogen peroxide on permeabilized rabbit psoas muscle fibers, focusing on changes in myosin purified from these fibers. Oxidation by 5 mM peroxide decreased fiber contractility (isometric force and shortening velocity) without significant changes in the enzymatic activity of myofibrils and isolated myosin. The inhibitory effects were reversed by treating fibers with dithiothreitol. Oxidation by 50 mM peroxide had a more pronounced and irreversible inhibitory effect on fiber contractility and also affected enzymatic activity of myofibrils, myosin, and actomyosin. Peroxide treatment also affected regulation of contractility, resulting in fiber activation in the absence of calcium. Electron paramagnetic resonance of spin-labeled myosin in muscle fibers showed that oxidation increased the fraction of myosin heads in the strong-binding structural state under relaxing conditions (low calcium) but had no effect under activating conditions (high calcium). This change in the distribution of structural states of myosin provides a plausible explanation for the observed changes in both contractile and regulatory functions. Mass spectroscopy analysis showed that 50 mM but not 5 mM peroxide induced oxidative modifications in both isoforms of the essential light chains and in the heavy chain of myosin subfragment 1 by targeting multiple methionine residues. We conclude that1) inhibition of muscle fiber contractility via oxidation of myosin occurs at high but not low concentrations of peroxide and2) the inhibitory effects of oxidation suggest a critical and previously unknown role of methionines in myosin function.
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解析收缩肌肉中自旋标记肌球蛋白的三种结构状态。
DOI：
10.1016/s0006-3495(95)79888-5
发表时间：
1995
期刊：
Biophysical journal.
影响因子：
--
作者：
Ostap,EM;Barnett,VA;Thomas,DD
通讯作者：
Thomas,DD
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影响因子：
2.9
作者：
H. Trayer;I. Trayer
通讯作者：
I. Trayer
肌球蛋白亚片段1同工酶的肌动蛋白激活及肌球蛋白轻链作用的研究。
DOI：
--
发表时间：
1979
期刊：
European Journal of Biochemistry
影响因子：
--
作者：
Paul D. Wagner;Cecilia S. Slater;B. Pope;A. Weeds
通讯作者：
A. Weeds
大鼠骨骼肌肌浆网Ca-ATP酶的体内衰老。
DOI：
10.1016/s0005-2736(97)00125-9
发表时间：
1997
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Viner,RI;Ferrington,DA;Aced,GI;Miller-Schlyer,M;Bigelow,DJ;Schöneich,C
通讯作者：
Schöneich,C
[10] 肌球蛋白的巯基修饰和标记
影响因子：
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作者：
E. Reisler
通讯作者：
E. Reisler