Decker Robert S, Decker Marlene L, Kulikovskaya Irina, Nakamura Sakie, Lee Daniel C, Harris Kathleen, Klocke Francis J, Winegrad Saul
Feinberg Cardiovascular Research Institute, Tarry 12-733, Feinberg School of Medicine, Northwestern University, 303 E Chicago Ave, Chicago, IL 60611-3008, USA.
Circulation. 2005 Feb 22;111(7):906-12. doi: 10.1161/01.CIR.0000155609.95618.75. Epub 2005 Feb 7.
Contractile dysfunction develops in the chronically instrumented canine myocardium after bouts of low-flow ischemia and persists after reperfusion. The objective of this study is to identify whether changes in the phosphorylation state of myosin-binding protein C (MyBP-C) are a potential cause of dysfunction.
During low-flow ischemia, MyBP-C is dephosphorylated, and the number of actomyosin cross-bridges in the central core of the sarcomere decreases as thick filaments dissemble from the periphery of the myofibril. During reperfusion, MyBP-C remains dephosphorylated, and its degradation is accelerated.
Dephosphorylation of MyBP-C may initiate changes in myofibril thick filament structure that decrease the interaction of myosin heads with actin thin filaments. Limiting the formation of actomyosin cross-bridges may contribute to the contractile dysfunction that is apparent after low-flow ischemia. Breakdown of MyBP-C during reperfusion may prolong myocardial stunning.
在经历多次低流量缺血发作后，长期植入仪器的犬类心肌会出现收缩功能障碍，且在再灌注后仍持续存在。本研究的目的是确定肌球蛋白结合蛋白C（MyBP-C）磷酸化状态的变化是否是功能障碍的潜在原因。
在低流量缺血期间，MyBP-C发生去磷酸化，随着粗肌丝从肌原纤维周边解离，肌节中央核心中的肌动球蛋白横桥数量减少。在再灌注期间，MyBP-C仍处于去磷酸化状态，其降解加速。
MyBP-C的去磷酸化可能引发肌原纤维粗肌丝结构的变化，从而减少肌球蛋白头部与肌动蛋白细肌丝的相互作用。限制肌动球蛋白横桥的形成可能导致低流量缺血后明显的收缩功能障碍。再灌注期间MyBP-C的分解可能会延长心肌顿抑。
