Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols.
Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols.
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DOI：
10.1371/journal.pone.0011209
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发表时间：
2010-06-18
期刊：
影响因子：
3.7
通讯作者：
Guilford WH
中科院分区：
文献类型：
--
作者：
Evangelista AM;Rao VS;Filo AR;Marozkina NV;Doctor A;Jones DR;Gaston B;Guilford WH
一氧化氮（NO）通过鸟苷酸环化酶的活化和蛋白质中半胱氨酸的修饰产生S-亚硝基硫醇来影响肌肉收缩。虽然NO直接影响收缩器，但靶肌原纤维蛋白的身份仍然未知。在这里，我们报告，氮氧化物直接调节横纹肌肌球蛋白。骨骼肌和心肌肌球蛋白暴露于生理浓度的氮氧化物，包括内源性亚硝基巯基S-亚硝基-L-半胱氨酸，以剂量依赖性和氧依赖性方式降低肌动蛋白丝在肌球蛋白上的速度，导致在激光陷阱换能器中测量的力加倍，并导致肌球蛋白重链中半胱氨酸的S-亚硝基化。在S-亚硝基-D-半胱氨酸的反应中没有观察到这些生物力学效应，这证明了对天然存在的异构体的特异性。大鼠肌球蛋白重链亚型和人心肌肌球蛋白重链在体内均被S-亚硝基化。这些数据表明，亚硝基化信号作为一个分子的“换档”肌球蛋白一个全新的机制，横纹肌和细胞的生物力学可能受到调节。
Nitric oxide (NO) has long been recognized to affect muscle contraction, both through activation of guanylyl cyclase and through modification of cysteines in proteins to yield S-nitrosothiols. While NO affects the contractile apparatus directly, the identities of the target myofibrillar proteins remain unknown. Here we report that nitrogen oxides directly regulate striated muscle myosins. Exposure of skeletal and cardiac myosins to physiological concentrations of nitrogen oxides, including the endogenous nitrosothiol S-nitroso-L-cysteine, reduced the velocity of actin filaments over myosin in a dose-dependent and oxygen-dependent manner, caused a doubling of force as measured in a laser trap transducer, and caused S-nitrosylation of cysteines in the myosin heavy chain. These biomechanical effects were not observed in response to S-nitroso-D-cysteine, demonstrating specificity for the naturally occurring isomer. Both myosin heavy chain isoforms in rats and cardiac myosin heavy chain from human were S-nitrosylated in vivo. These data show that nitrosylation signaling acts as a molecular “gear shift” for myosin—an altogether novel mechanism by which striated muscle and cellular biomechanics may be regulated.
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影响因子：
5.5
作者：
Andrade, FH;Reid, MB;Westerblad, H
通讯作者：
Westerblad, H
DOI：
10.1152/ajpcell.1997.273.4.c1371
发表时间：
1997-10-01
影响因子：
5.5
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4.5
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影响因子：
3.3
作者：
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通讯作者：
Sieck, GC