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

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...

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Main Authors:	Zheng, Wei-Wan, Li, Xin-Yuan, Liu, Hui-Bin, Wang, Zi-Rui, Hu, Qing-Qing, Li, Yu-Xia, Song, Bin-Lin, Lou, Jie, Wang, Qiu-Shi, Ma, He-Ping, Zhang, Zhi-Ren
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011216/

id	pubmed-5011216
recordtype	oai_dc
spelling	pubmed-50112162016-09-15 AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells Zheng, Wei-Wan Li, Xin-Yuan Liu, Hui-Bin Wang, Zi-Rui Hu, Qing-Qing Li, Yu-Xia Song, Bin-Lin Lou, Jie Wang, Qiu-Shi Ma, He-Ping Zhang, Zhi-Ren Research Article 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 (P O). 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 P O. 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. Hindawi Publishing Corporation 2016 2016-08-22 /pmc/articles/PMC5011216/ /pubmed/27635187 http://dx.doi.org/10.1155/2016/1531392 Text en Copyright © 2016 Wei-Wan Zheng et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zheng, Wei-Wan Li, Xin-Yuan Liu, Hui-Bin Wang, Zi-Rui Hu, Qing-Qing Li, Yu-Xia Song, Bin-Lin Lou, Jie Wang, Qiu-Shi Ma, He-Ping Zhang, Zhi-Ren
spellingShingle	Zheng, Wei-Wan Li, Xin-Yuan Liu, Hui-Bin Wang, Zi-Rui Hu, Qing-Qing Li, Yu-Xia Song, Bin-Lin Lou, Jie Wang, Qiu-Shi Ma, He-Ping Zhang, Zhi-Ren AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
author_facet	Zheng, Wei-Wan Li, Xin-Yuan Liu, Hui-Bin Wang, Zi-Rui Hu, Qing-Qing Li, Yu-Xia Song, Bin-Lin Lou, Jie Wang, Qiu-Shi Ma, He-Ping Zhang, Zhi-Ren
author_sort	Zheng, Wei-Wan
title	AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
title_short	AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
title_full	AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
title_fullStr	AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
title_full_unstemmed	AMP-Activated Protein Kinase Attenuates High Salt-Induced Activation of Epithelial Sodium Channels (ENaC) in Human Umbilical Vein Endothelial Cells
title_sort	amp-activated protein kinase attenuates high salt-induced activation of epithelial sodium channels (enac) in human umbilical vein endothelial cells
description	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 (P O). 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 P O. 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.
publisher	Hindawi Publishing Corporation
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011216/
_version_	1613643239065124864

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

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