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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The anti-apoptotic protein HAX-1 is a regulator of cardiac function
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The anti-apoptotic protein HAX-1 is a regulator of cardiac function

机译：抗凋亡蛋白HAX-1是心脏功能的调节剂

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摘要

The HS-1 associated protein X-1 (HAX-1) is a ubiquitously expressed protein that protects cardiomyocytes from programmed cell death. Here we identify HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics. Conversely, downregulation of HAX-1 enhanced calcium cycling and contractility. The inhibitory effects of HAX-1 were abolished upon phosphorylation of phospholamban, which plays a fundamental role in controlling basal contractility and constitutes a key downstream effector of the β-adrenergic signaling cascade. Mechanistically, HAX-1 promoted formation of phospholamban monomers, the active/inhibitory units of the calcium pump. Indeed, ablation of PLN rescued HAX-1 inhibition of contractility in vivo. Thus, HAX-1 represents a regulatory mechanism in cardiac calcium cycling and its responses to sympathetic stimulation, implicating its importance in calcium homeostasis and cell survival.
机译：HS-1相关蛋白X-1（HAX-1）是一种普遍表达的蛋白，可保护心肌细胞免受程序性细胞死亡。在这里，我们将HAX-1识别为心脏收缩力和钙循环的调节剂。 HAX-1的过表达降低了离体心肌细胞和体内肌浆网Ca-ATPase（SERCA2）泵的活性，导致心肌细胞钙动力学和力学降低。相反，HAX-1的下调可增强钙循环和收缩力。 HAX-1的抑制作用在磷酸lamban的磷酸化作用后被取消，后者在控制基础收缩中起着基本作用，并构成了β-肾上腺素信号级联反应的关键下游效应物。从机理上讲，HAX-1促进了磷酸lamban单体（钙泵的活性/抑制单元）的形成。实际上，PLN的消融挽救了HAX-1对体内收缩力的抑制作用。因此，HAX-1代表心脏钙循环及其对交感神经刺激的反应的调节机制，暗示其在钙稳态和细胞存活中的重要性。

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  • 作者

    Wen Zhao; Jason R. Waggoner; Zhi-Guo Zhang; Chi Keung Lam; Peidong Han; Jiang Qian; Paul M. Schroder; Bryan Mitton; Aikaterini Kontrogianni-Konstantopoulos; Seth L. Robia; Evangelia G. Kranias;

  • 作者单位

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575 Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China, 100083;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575;

    Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201;

    Department of Physiology, Loyola University Chicago, Maywood, IL 60153;

    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0575 Molecular Biology Divisions, Center for Basic Research, Foundation for Biomedical Research of the Academy of Athens, Athens 115 27, Greece;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    calcium; cardiomyocytes; contractility; phospholamban; sarcoplasmic reticulum;

    机译：钙;心肌细胞收缩力磷lamban肌质网;

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