Differential roles of caveolin-1 in ouabain-induced Na+/K+-ATPase cardiac signaling and contractility

Author:

Bai Yan12,Wu Jian1,Li Daxiang13,Morgan Eric E.4,Liu Jiang5,Zhao Xiaochen6,Walsh Aaron1,Saikumar Jagannath6,Tinkel Jodi7,Joe Bina64,Gupta Rajesh7,Liu Lijun174

Affiliation:

1. Department of Biochemistry and Cancer Biology, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio;

2. Pediatrics Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China;

3. State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, Anhui, China; and

4. Center for Hypertension and Personalized Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio;

5. Department of Pharmacology, Physiology and Toxicology, JCE School of Medicine, Marshall University, Huntington, West Virginia

6. Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio;

7. Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio;

Abstract

Binding of ouabain to cardiac Na+/K+-ATPase initiates cell signaling and causes contractility in cardiomyocytes. It is widely accepted that caveolins, structural proteins of caveolae, have been implicated in signal transduction. It is known that caveolae play a role in Na+/K+-ATPase functions. Regulation of caveolin-1 in ouabain-mediated cardiac signaling and contractility has never been reported. The aim of this study is to compare ouabain-induced cardiac signaling and contractility in wild-type (WT) and caveolin-1 knockout (cav-1 KO) mice. In contrast with WT cardiomyocytes, ouabain-induced signaling e.g., activation of phosphoinositide 3-kinase-α/Akt and extracellular signal-regulated kinases (ERK)1/2, and hypertrophic growth were significantly reduced in cav-1 KO cardiomyocytes. Interactions of the Na+/K+-ATPase α1-subunit with caveolin-3 and the Na+/K+-ATPase α1-subunit with PI3K-α were also decreased in cav-1 KO cardiomyocytes. The results from cav-1 KO mouse embryonic fibroblasts also proved that cav-1 significantly attenuated ouabain-induced ERK1/2 activation without alteration in protein and cholesterol distribution in caveolae/lipid rafts. Intriguingly, the effect of ouabain induced positive inotropy in vivo (via transient infusion of ouabain, 0.48 nmol/g body wt) was not attenuated in cav-1 KO mice. Furthermore, ouabain (1–100 μM) induced dose-dependent contractility in isolated working hearts from WT and cav-1 KO mice. The effects of ouabain on contractility between WT and cav-1 KO mice were not significantly different. These results demonstrated differential roles of cav-1 in the regulation of ouabain signaling and contractility. Signaling by ouabain, in contrast to contractility, may be a redundant property of Na+/K+-ATPase.

Funder

HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)

National Natural Science Foundation of China (NSFC)

Publisher

American Physiological Society

Subject

Genetics,Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3