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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-64762

Yakushev, S; Band, M; Tissot van Patot, M; Gassmann, M; Avivi, A; Bogdanova, A (2012). Cross-talk between S-nitrosylation and S-glutathionylation in control of the Na,K-ATPase regulation in hypoxic heart. AJP - Heart and Circulatory Physiology, 303(11):H1332-43.

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Abstract

Oxygen-induced regulation of Na,K-ATPase was studied in rat myocardium. In rat heart Na,K-ATPase responded to hypoxia with a dose-dependent inhibition in hydrolytic activity. Inhibition of Na,K-ATPase in hypoxic rat heart was associated with decrease in NO production and progressive oxidative stress. Accumulation of oxidized glutathione (GSSG) and decrease in NO availability in hypoxic rat heart were followed by a decrease in S-nitrosylation and up-regulation of S-glutathionylation of the catalytic α subunit of the Na,K-ATPase. Induction of S-glutathionylation of the α subunit by treatment of tissue homogenate with GSSG resulted in complete inhibition of the enzyme in rat a myocardial tissue homogenate. Inhibitory effect of GSSG in rat sarcolemma could be significantly decreased upon activation of NO synthases. we have further tested if oxidative stress and suppression of the Na,K-ATPase activity are observed in hypoxic heart of two subterranean hypoxia-tolerant blind mole species (Spalax galili and Spalax judaei). In both hypoxia tolerant Spalax species activity of the enzyme and tissue redox state were maintained under hypoxic conditions. However, localisation of cysteines within the catalytic subunit of the Na,K-ATPase was preserved and induction of S-glutathionylation by GSSG in tissue homogenate inhibited the Spalax ATPase as efficiently as in rat heart. The obtained data indicate that oxygen-induced regulation of the Na,K-ATPase in the heart is mediated by a switch between S-glutathionylation and S-nitrosylation of the regulatory thiol groups localized at the catalytic subunit of the enzyme.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:20 Sep 2012 17:01
Last Modified:08 Dec 2013 16:37
Publisher:American Physiological Society
ISSN:0363-6135
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1152/ajpheart.00145.2012
PubMed ID:22982781
Citations:Web of Science®. Times Cited: 3
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