Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-018-31460-z
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dc.titleDR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury
dc.contributor.authorHua F.
dc.contributor.authorWu Z.
dc.contributor.authorYan X.
dc.contributor.authorZheng J.
dc.contributor.authorSun H.
dc.contributor.authorCao X.
dc.contributor.authorBian J.-S.
dc.date.accessioned2019-03-08T01:10:43Z
dc.date.available2019-03-08T01:10:43Z
dc.date.issued2018-12-01
dc.identifier.citationHua F., Wu Z., Yan X., Zheng J., Sun H., Cao X., Bian J.-S. (2018-12-01). DR region of Na+-K+-ATPase is a new target to protect heart against oxidative injury. Scientific Reports 8 (1) : 13100. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-018-31460-z
dc.identifier.issn2045-2322
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/152073
dc.description.abstractPrevious 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. � 2018, The Author(s).
dc.publisherNature Publishing Group
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1038/s41598-018-31460-z
dc.description.sourcetitleScientific Reports
dc.description.volume8
dc.description.issue1
dc.description.page13100
dc.published.statepublished
dc.grant.idNMRC/1274/2010
dc.grant.idNSFC 81872865
dc.grant.fundingagencySingapore National Medical Research Council Fund
dc.grant.fundingagencyNational Nature Science Foundation of China
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