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Author Notes:

Correspondence should be addressed to Hui-Bin Liu; liuhuibin66@126.com and Zhi-Ren Zhang; zhirenz@yahoo.com.

Wei-Wan Zheng and Xin-Yuan Li contributed equally to this work.

The authors declare that there are no competing interests regarding the publication of this paper.

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Research Funding:

This study was supported by Key Project of Chinese National Program for Fundamental Research and Development (973 Program, 2014CB542401, and 2012CB517803 to Zhi-Ren Zhang), National Natural Science Foundation of China (81270340 and 81320108002 to Zhi-Ren Zhang and 81300191 to Hui-Bin Liu) and Research Project of Health and Family Planning Commission of Heilongjiang Province (2014-330 to Bin-Lin Song).

This work was also partially supported by a grant from NIH (R01 DK 100582 to He-Ping Ma).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • NA+ CHANNEL
  • PLASMA SODIUM
  • LIDDLES-SYNDROME
  • DIETARY SALT
  • RELEASE
  • ALDOSTERONE
  • INHIBITION
  • EXPRESSION
  • TRANSPORT
  • ARTERIES

AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells

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Journal Title:

Oxidative Medicine and Cellular Longevity

Volume:

Volume 2016

Publisher:

, Pages 1531392-1531392

Type of Work:

Article | Final Publisher PDF

Abstract:

Recent studies suggest that the epithelial sodium channel (ENaC) is expressed in the endothelial cells. To test whether high salt affects the NO production via regulation of endothelial ENaC, human umbilical vein endothelial cells (HUVECs) were incubated in solutions containing either normal or high sodium (additional 20 mM NaCl). Our data showed that high sodium treatment significantly increased α-, β-, and γ-ENaC expression levels in HUVECs. Using the cell-attached patch-clamp technique, we demonstrated that high sodium treatment significantly increased ENaC open probability (PO). Moreover, nitric oxide synthase (eNOS) phosphorylation (Ser 1177) levels and NO production were significantly decreased by high sodium in HUVECs; the effects of high sodium on eNOS phosphorylation and NO production were inhibited by a specific ENaC blocker, amiloride. Our results showed that high sodium decreased AMP-activated kinase (AMPK) phosphorylation in endothelial cells. On the other hand, metformin, an AMPK activator, prevented high sodium-induced upregulation of ENaC expression and PO. Moreover, metformin prevented high salt-induced decrease in NO production and eNOS phosphorylation. These results suggest that high sodium stimulates ENaC activation by negatively modulating AMPK activity, thereby leading to reduction in eNOS activity and NO production in endothelial cells.

Copyright information:

© 2016 Wei-Wan Zheng et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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