DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury

Abstract Previous studies have shown that the activity and expression of Na+/K+-ATPase (NKA) are down-regulated in the failing hearts, and that an antibody against the DR-region of NKA (DR-Ab) can stimulate its activity. The present study was designed to investigate the beneficial effects of this an...

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Autores principales:	Fei Hua, Zhiyuan Wu, Xiaofei Yan, Jin Zheng, Haijian Sun, Xu Cao, Jin-Song Bian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1da50230ff634439a703822775590be7
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spelling	oai:doaj.org-article:1da50230ff634439a703822775590be72021-12-02T15:07:51ZDR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury10.1038/s41598-018-31460-z2045-2322https://doaj.org/article/1da50230ff634439a703822775590be72018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31460-zhttps://doaj.org/toc/2045-2322Abstract Previous studies have shown that the activity and expression of Na+/K+-ATPase (NKA) are down-regulated in the failing hearts, and that an antibody against the DR-region of NKA (DR-Ab) can stimulate its activity. The present study was designed to investigate the beneficial effects of this antibody against cardiac injury and the underlying mechanisms. We found that DR-Ab improved cardiac function, alleviated cardiac hypertrophy and reduced oxidative stress in isoproterenol-treated mice. In AC16 human cardiomyocytes, DR-Ab increased cell viability and attenuated apoptosis under oxidative stress. Corresponding to the observation of reduced NKA activity, NKA abundance on plasma membrane was lowered during oxidative stress. Suppressed activity of protein phosphatase 2 A (PP2A) was responsible for the loss of membrane NKA due to the increased phosphorylation of key serine residues that trigger endocytosis. Incubation with DR-Ab restored PP2A activity and stabilized NKA expression on the plasma membrane. Inhibitors of PP2A abolished the protective effect of DR-Ab against oxidative stress. In summary, our data indicate that loss of membrane NKA may contribute to cardiac pathologies in heart failure. DR-Ab, by stabilizing membrane NKA, protects cardiomyocytes against oxidative injury and improves cardiac function in the failing hearts, suggesting a novel approach to treat heart failure.Fei HuaZhiyuan WuXiaofei YanJin ZhengHaijian SunXu CaoJin-Song BianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fei Hua Zhiyuan Wu Xiaofei Yan Jin Zheng Haijian Sun Xu Cao Jin-Song Bian DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
description	Abstract Previous studies have shown that the activity and expression of Na+/K+-ATPase (NKA) are down-regulated in the failing hearts, and that an antibody against the DR-region of NKA (DR-Ab) can stimulate its activity. The present study was designed to investigate the beneficial effects of this antibody against cardiac injury and the underlying mechanisms. We found that DR-Ab improved cardiac function, alleviated cardiac hypertrophy and reduced oxidative stress in isoproterenol-treated mice. In AC16 human cardiomyocytes, DR-Ab increased cell viability and attenuated apoptosis under oxidative stress. Corresponding to the observation of reduced NKA activity, NKA abundance on plasma membrane was lowered during oxidative stress. Suppressed activity of protein phosphatase 2 A (PP2A) was responsible for the loss of membrane NKA due to the increased phosphorylation of key serine residues that trigger endocytosis. Incubation with DR-Ab restored PP2A activity and stabilized NKA expression on the plasma membrane. Inhibitors of PP2A abolished the protective effect of DR-Ab against oxidative stress. In summary, our data indicate that loss of membrane NKA may contribute to cardiac pathologies in heart failure. DR-Ab, by stabilizing membrane NKA, protects cardiomyocytes against oxidative injury and improves cardiac function in the failing hearts, suggesting a novel approach to treat heart failure.
format	article
author	Fei Hua Zhiyuan Wu Xiaofei Yan Jin Zheng Haijian Sun Xu Cao Jin-Song Bian
author_facet	Fei Hua Zhiyuan Wu Xiaofei Yan Jin Zheng Haijian Sun Xu Cao Jin-Song Bian
author_sort	Fei Hua
title	DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
title_short	DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
title_full	DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
title_fullStr	DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
title_full_unstemmed	DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
title_sort	dr region of na+-k+-atpase is a new target to protect heart against oxidative injury
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1da50230ff634439a703822775590be7
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_version_	1718388370087870464

DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury

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