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J Membr Biol
2010 Aug 01;2363:259-70. doi: 10.1007/s00232-010-9297-7.
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Stimulation of ENaC activity by rosiglitazone is PPARγ-dependent and correlates with SGK1 expression increase.
Renauld S
,
Tremblay K
,
Ait-Benichou S
,
Simoneau-Roy M
,
Garneau H
,
Staub O
,
Chraïbi A
.
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Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists used to treat type 2 diabetes. TZD treatment induces side effects such as peripheral fluid retention, often leading to discontinuation of therapy. Previous studies have shown that PPARγ activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC) through different mechanisms. However, the effect of TZDs on ENaC activity is not clearly understood. Here, we show that treating Xenopus laevis oocytes expressing ENaC and PPARγ with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium current (Iam), as measured by two-electrode voltage clamp. RGZ-induced ENaC activation was PPARγ-dependent since the PPARγ antagonist GW9662 blocked the activation. The RGZ-induced Iam increase was not mediated through direct serum- and glucocorticoid-regulated kinase (SGK1)-dependent phosphorylation of serine residue 594 on the human ENaC α-subunit but by the diminution of ENaC ubiquitination through the SGK1/Nedd4-2 pathway. In accordance, RGZ increased the activity of ENaC by enhancing its cell surface expression, most probably indirectly mediated through the increase of SGK1 expression.
Abriel,
Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome.
1999, Pubmed,
Xenbase
Abriel,
Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome.
1999,
Pubmed
,
Xenbase
Alvarez de la Rosa,
The serum and glucocorticoid kinase sgk increases the abundance of epithelial sodium channels in the plasma membrane of Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Artunc,
Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARgamma agonist pioglitazone.
2008,
Pubmed
Bens,
Regulation of NaCl transport in the renal collecting duct: lessons from cultured cells.
2006,
Pubmed
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Canessa,
Epithelial sodium channel related to proteins involved in neurodegeneration.
1993,
Pubmed
,
Xenbase
Chraïbi,
Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Collino,
The selective PPARgamma antagonist GW9662 reverses the protection of LPS in a model of renal ischemia-reperfusion.
2005,
Pubmed
Debonneville,
Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.
2001,
Pubmed
,
Xenbase
Diakov,
A novel pathway of epithelial sodium channel activation involves a serum- and glucocorticoid-inducible kinase consensus motif in the C terminus of the channel's alpha-subunit.
2004,
Pubmed
,
Xenbase
Fajas,
PPARgamma3 mRNA: a distinct PPARgamma mRNA subtype transcribed from an independent promoter.
1998,
Pubmed
Fajas,
The organization, promoter analysis, and expression of the human PPARgamma gene.
1997,
Pubmed
Feige,
From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions.
2006,
Pubmed
Fejes-Tóth,
Epithelial Na+ channel activation and processing in mice lacking SGK1.
2008,
Pubmed
Forman,
15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.
1995,
Pubmed
Freundlich,
A novel epithelial sodium channel beta-subunit mutation associated with hypertensive Liddle syndrome.
2005,
Pubmed
Frindt,
Na channels in the rat connecting tubule.
2004,
Pubmed
Füchtenbusch,
Clinical efficacy of new thiazolidinediones and glinides in the treatment of type 2 diabetes mellitus.
2000,
Pubmed
Guan,
Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans.
1997,
Pubmed
Guan,
Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption.
2005,
Pubmed
Hansson,
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.
1995,
Pubmed
,
Xenbase
Hirsch,
Pulmonary edema associated with troglitazone therapy.
,
Pubmed
Hong,
PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells.
2003,
Pubmed
Kamynina,
A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel.
2001,
Pubmed
,
Xenbase
Lang,
The physiological impact of the serum and glucocorticoid-inducible kinase SGK1.
2009,
Pubmed
Lang,
(Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms.
2006,
Pubmed
Lee,
Regulation of epithelial Na+ channels by aldosterone: role of Sgk1.
2008,
Pubmed
Lehmann,
An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).
1995,
Pubmed
Lifton,
Molecular genetics of human blood pressure variation.
1996,
Pubmed
Loffing,
Regulated sodium transport in the renal connecting tubule (CNT) via the epithelial sodium channel (ENaC).
2009,
Pubmed
Nofziger,
PPARgamma agonists do not directly enhance basal or insulin-stimulated Na(+) transport via the epithelial Na(+) channel.
2005,
Pubmed
,
Xenbase
Pavlov,
Peroxisome proliferator-activated receptor gamma antagonists decrease Na+ transport via the epithelial Na+ channel.
2009,
Pubmed
Renauld,
Ile481 from the guinea pig alpha-subunit plays a major role in the activation of ENaC by cpt-cAMP.
2008,
Pubmed
,
Xenbase
Renauld,
Role of the C-terminal part of the extracellular domain of the alpha-ENaC in activation by sulfonylurea glibenclamide.
2009,
Pubmed
,
Xenbase
Riazi,
Rosiglitazone regulates ENaC and Na-K-2Cl cotransporter (NKCC2) abundance in the obese Zucker rat.
2006,
Pubmed
Ruan,
PPARs and the kidney in metabolic syndrome.
2008,
Pubmed
Saad,
The role of Sgk-1 in the upregulation of transport proteins by PPAR-{gamma} agonists in human proximal tubule cells.
2009,
Pubmed
Shimkets,
Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.
1994,
Pubmed
Snyder,
Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel.
2002,
Pubmed
Snyder,
Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel.
1995,
Pubmed
,
Xenbase
Song,
Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats.
2004,
Pubmed
Spraggs,
Genetic variants in the epithelial sodium channel associate with oedema in type 2 diabetic patients receiving the peroxisome proliferator-activated receptor gamma agonist farglitazar.
2007,
Pubmed
Staub,
Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination.
1997,
Pubmed
,
Xenbase
Staub,
Impact of Nedd4 proteins and serum and glucocorticoid-induced kinases on epithelial Na+ transport in the distal nephron.
2005,
Pubmed
Staub,
WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome.
1996,
Pubmed
Taruno,
Intracellular calcium plays a role as the second messenger of hypotonic stress in gene regulation of SGK1 and ENaC in renal epithelial A6 cells.
2008,
Pubmed
,
Xenbase
Thomas,
Pulmonary edema associated with rosiglitazone and troglitazone.
2001,
Pubmed
Thomas,
New insights into epithelial sodium channel function in the kidney: site of action, regulation by ubiquitin ligases, serum- and glucocorticoid-inducible kinase and proteolysis.
2004,
Pubmed
Tontonoz,
Fat and beyond: the diverse biology of PPARgamma.
2008,
Pubmed
Vallon,
New insights into the role of serum- and glucocorticoid-inducible kinase SGK1 in the regulation of renal function and blood pressure.
2005,
Pubmed
Willson,
Peroxisome proliferator-activated receptor gamma and metabolic disease.
2001,
Pubmed
Wulff,
Impaired renal Na(+) retention in the sgk1-knockout mouse.
2002,
Pubmed
,
Xenbase
Yang,
Renal and vascular mechanisms of thiazolidinedione-induced fluid retention.
2008,
Pubmed
Zacchia,
Nephrotic syndrome: new concepts in the pathophysiology of sodium retention.
2008,
Pubmed
Zhang,
Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention.
2005,
Pubmed