Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology.
Role of protein phosphatase-1 inhibitor-1 in cardiac physiology and pathophysiology.
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DOI：
10.1016/j.yjmcc.2009.05.010
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发表时间：
2009-09
影响因子：
5
通讯作者：
Kranias, Evangelia G.
中科院分区：
文献类型：
--
作者：
Nicolaou, Persoulla;Hajjar, Roger J.;Kranias, Evangelia G.
1型蛋白磷酸酶（PP 1）是心肌细胞中Ca 2+循环和收缩性的关键负调节剂。特别是，在β-肾上腺素能刺激后，通过使关键磷酸化蛋白脱磷酸化，介导心脏功能恢复至基础水平。PP 1是由其催化亚基和辅助亚基组成的全酶。这些调节蛋白决定了PP 1的亚细胞定位、底物特异性和活性。其中，抑制剂-1是特别重要的，因为它已被牵连作为多个神经激素途径，精细地调节PP 1活性，在肌浆网（SR）的水平上的集成器。事实上，干扰PP 1的调节抑制剂-1已牵连在心力衰竭的发病机制，这表明抑制剂-1为基础的治疗干预措施，可以改善心脏功能障碍和重塑衰竭的心脏。本文就抑制剂-1在心脏生理学中的作用、对心脏疾病的可能作用及其作为一种新的治疗策略的潜力作一综述。
The type 1 protein phosphatase (PP1) is a critical negative regulator of Ca2+ cycling and contractility in the cardiomyocyte. In particular, it mediates restoration of cardiac function to basal levels, after β-adrenergic stimulation, by dephosphorylating key phospho-proteins. PP1 is a holoenzyme comprised of its catalytic and auxiliary subunits. These regulatory proteins dictate PP1's subcellular localization, substrate specificity and activity. Amongst them, inhibitor-1 is of particular importance since it has been implicated as an integrator of multiple neurohormonal pathways, which finely regulate PP1 activity, at the level of the sarcoplasmic reticulum (SR). In fact, perturbations in the regulation of PP1 by inhibitor-1 have been implicated in the pathogenesis of heart failure, suggesting that inhibitor-1-based therapeutic interventions may ameliorate cardiac dysfunction and remodeling in the failing heart. This review will discuss the current views on the role of inhibitor-1 in cardiac physiology, its possible contribution to cardiac disease and its potential as a novel therapeutic strategy.
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影响因子：
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作者：
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