Elkrief Daren, Cheng Yu-Shu, Matusovsky Oleg S, Rassier Dilson E
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada.
Am J Physiol Cell Physiol. 2022 Oct 1;323(4):C1206-C1214. doi: 10.1152/ajpcell.00427.2021. Epub 2022 Sep 5.
The interaction between actin and myosin is the basis of contraction and force production in muscle fibers. Studies have shown that actin and myosin oxidation cause myofibrillar weakness in healthy and diseased muscles. The degree to which oxidation of each of these proteins contributes to an attenuated force in myofibrils is unclear. In this study, we show that exposure of actin and myosin to the chemical 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1), an NO and O donor, affected actin-myosin interactions, as shown by a decreased myosin-propelled actin velocity in the in vitro motility assay. We also observed that oxidation of actin and myosin resulted in a decrease in force generated by myosin and actin filaments, as determined by a system of microfabricated cantilevers. Although myosin is more sensitive to oxidative modifications than actin, as indicated by a steeper decrease in velocity and force by the filaments, modifications on actin are sufficient to affect force and velocity and also contribute to a decrease in contractile activity in muscles.
肌动蛋白和肌球蛋白之间的相互作用是肌肉纤维收缩和产生力量的基础。研究表明，肌动蛋白和肌球蛋白氧化会导致健康和患病肌肉中的肌原纤维功能减弱。这些蛋白质各自的氧化对肌原纤维中力量减弱的贡献程度尚不清楚。在本研究中，我们发现，肌动蛋白和肌球蛋白暴露于化学物质5-氨基-3-(4-吗啉基)-1,2,3-恶二唑鎓氯化物（SIN-1，一种一氧化氮和氧供体）会影响肌动蛋白-肌球蛋白相互作用，体外运动分析显示肌球蛋白推动肌动蛋白的速度降低。我们还观察到，通过微制造悬臂系统测定，肌动蛋白和肌球蛋白的氧化导致肌球蛋白和肌动蛋白丝产生的力量下降。尽管如丝的速度和力量下降更显著所示，肌球蛋白比肌动蛋白对氧化修饰更敏感，但肌动蛋白上的修饰足以影响力量和速度，也会导致肌肉收缩活动下降。
