Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Cell Physiol
2012 Dec 01;30311:C1129-38. doi: 10.1152/ajpcell.00139.2012.
Show Gene links
Show Anatomy links
Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species.
Bao HF
,
Song JZ
,
Duke BJ
,
Ma HP
,
Denson DD
,
Eaton DC
.
???displayArticle.abstract???
Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distalnephron cells. The data showed that ethanol significantly increased both ENaC open probability (P(o)) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased α-ENaC protein in the apical membrane. The effects of ethanol on ENaC P(o) and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde.
Assadi,
Acute effect of ethanol on renal electrolyte excretion in rats.
1989, Pubmed
Assadi,
Acute effect of ethanol on renal electrolyte excretion in rats.
1989,
Pubmed
Bailey,
Acute and chronic ethanol increases reactive oxygen species generation and decreases viability in fresh, isolated rat hepatocytes.
1998,
Pubmed
Castellano,
Role of RAS in the regulation of PI 3-kinase.
2010,
Pubmed
Castellano,
Functional specificity of ras isoforms: so similar but so different.
2011,
Pubmed
Castellano,
RAS Interaction with PI3K: More Than Just Another Effector Pathway.
2011,
Pubmed
Chen,
Epithelial sodium channel regulated by aldosterone-induced protein sgk.
1999,
Pubmed
,
Xenbase
Debonneville,
Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.
2001,
Pubmed
,
Xenbase
Deng,
Putative role of brain acetaldehyde in ethanol addiction.
2008,
Pubmed
Downes,
Stimulation of PI 3-kinase signaling via inhibition of the tumor suppressor phosphatase, PTEN.
2007,
Pubmed
Flores,
The role of Nedd4/Nedd4-like dependant ubiquitylation in epithelial transport processes.
2003,
Pubmed
Guidot,
Ethanol ingestion impairs alveolar epithelial glutathione homeostasis and function, and predisposes to endotoxin-mediated acute lung injury.
1999,
Pubmed
Guidot,
Ethanol ingestion via glutathione depletion impairs alveolar epithelial barrier function in rats.
2000,
Pubmed
Heaton,
Ethanol-mediated generation of reactive oxygen species in developing rat cerebellum.
2002,
Pubmed
Helms,
Redox regulation of epithelial sodium channels examined in alveolar type 1 and 2 cells patch-clamped in lung slice tissue.
2008,
Pubmed
Helms,
Phosphatidylinositol 3,4,5-trisphosphate mediates aldosterone stimulation of epithelial sodium channel (ENaC) and interacts with gamma-ENaC.
2005,
Pubmed
Kohli,
Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway.
2007,
Pubmed
Leslie,
Redox regulation of PI 3-kinase signalling via inactivation of PTEN.
2003,
Pubmed
Leslie,
Redox regulation of phosphatase function.
2004,
Pubmed
Loffing,
Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK.
2001,
Pubmed
,
Xenbase
Ma,
Regulation of the epithelial sodium channel by phosphatidylinositides: experiments, implications, and speculations.
2007,
Pubmed
Ma,
Acute regulation of epithelial sodium channel by anionic phospholipids.
2005,
Pubmed
Ma,
Hydrogen peroxide stimulates the epithelial sodium channel through a phosphatidylinositide 3-kinase-dependent pathway.
2011,
Pubmed
,
Xenbase
Ma,
Anionic phospholipids regulate native and expressed epithelial sodium channel (ENaC).
2002,
Pubmed
,
Xenbase
Pearce,
The role of SGK1 in hormone-regulated sodium transport.
2001,
Pubmed
Pearce,
Role of SGK in mineralocorticoid-regulated sodium transport.
2000,
Pubmed
,
Xenbase
Pochynyuk,
Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides.
2006,
Pubmed
Rotin,
Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p family of ubiquitin-protein ligases.
2000,
Pubmed
Snyder,
Intoxicated Na(+) channels. Focus on "ethanol stimulates epithelial sodium channels by elevating reactive oxygen species".
2012,
Pubmed
Tai,
Reactive oxygen species (ROS) play a critical role in the cAMP-induced activation of Ras and the phosphorylation of ERK1/2 in Leydig cells.
2011,
Pubmed
Takemura,
Rac1-mediated NADPH oxidase release of O2- regulates epithelial sodium channel activity in the alveolar epithelium.
2010,
Pubmed
Venkatesan,
Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells.
2007,
Pubmed
Wang,
SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport.
2001,
Pubmed
,
Xenbase
Wu,
Alcohol, oxidative stress, and free radical damage.
2003,
Pubmed
Xiao,
Role of reactive oxygen species and NAD(P)H oxidase in alpha(1)-adrenoceptor signaling in adult rat cardiac myocytes.
2002,
Pubmed
Yu,
Aldosterone-induced increases in superoxide production counters nitric oxide inhibition of epithelial Na channel activity in A6 distal nephron cells.
2007,
Pubmed
,
Xenbase
Yu,
Single-channel analysis of functional epithelial sodium channel (ENaC) stability at the apical membrane of A6 distal kidney cells.
2008,
Pubmed
,
Xenbase
Yu,
Effect of divalent heavy metals on epithelial Na+ channels in A6 cells.
2007,
Pubmed
,
Xenbase
Yue,
Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells.
2002,
Pubmed
,
Xenbase
