Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.

Resveratrol, a naturally occurring phytoalexin, has reported cardioprotective, anti-inflammatory, chemopreventative and antidiabetic properties. Several studies indicate the multiple effects of resveratrol on cellular function are due to its inhibition of class 1A phosphoinositide 3-kinase (PI3K) me...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kelly M Weixel, Allison Marciszyn, Rodrigo Alzamora, Hui Li, Oliver Fischer, Robert S Edinger, Kenneth R Hallows, John P Johnson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa5b842b25724128a8ddd3c7ded65dd4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aa5b842b25724128a8ddd3c7ded65dd4
record_format	dspace
spelling	oai:doaj.org-article:aa5b842b25724128a8ddd3c7ded65dd42021-11-18T08:49:37ZResveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.1932-620310.1371/journal.pone.0078019https://doaj.org/article/aa5b842b25724128a8ddd3c7ded65dd42013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24205069/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Resveratrol, a naturally occurring phytoalexin, has reported cardioprotective, anti-inflammatory, chemopreventative and antidiabetic properties. Several studies indicate the multiple effects of resveratrol on cellular function are due to its inhibition of class 1A phosphoinositide 3-kinase (PI3K) mediated signaling pathways, but it also activates AMP-activated protein kinase (AMPK). As sodium transport in the kidney via the Epithelial Sodium Channel (ENaC) is highly sensitive to changes in phosphoinositide signaling in the membrane and AMPK, we employed resveratrol to probe the relative effects of phosphatidylinositol species in the plasma membrane and AMPK activity and their impact on ENaC activity in mouse cortical collecting duct (mpkCCDc14) cells. Here we demonstrate that resveratrol acutely reduces amiloride-sensitive current in mpkCCDc14 cells. The time course and dose dependency of this inhibition paralleled depletion of the PI(3,4,5)P3 reporter (AKT-PH) in live-cell microscopy, indicating the early inhibition is likely mediated by resveratrol's known effects on PI3K activity. Additionally, resveratrol induces a late inhibitory effect (4-24 hours) that appears to be mediated via AMPK activation. Resveratrol treatment induces significant AMPK activation compared with vehicle controls after 4 h, which persists through 16 h. Knockdown of AMPK or treatment with the AMPK inhibitor Compound C reduced the late phase of current reduction but had no effect on the early inhibitory activity of resveratrol. Collectively, these data demonstrate that resveratrol inhibits ENaC activity by a dual effect: an early reduction in activity seen within 5 minutes related to depletion of membrane PIP3, and a sustained late (4-24 h) effect secondary to activation of AMPK.Kelly M WeixelAllison MarciszynRodrigo AlzamoraHui LiOliver FischerRobert S EdingerKenneth R HallowsJohn P JohnsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e78019 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kelly M Weixel Allison Marciszyn Rodrigo Alzamora Hui Li Oliver Fischer Robert S Edinger Kenneth R Hallows John P Johnson Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
description	Resveratrol, a naturally occurring phytoalexin, has reported cardioprotective, anti-inflammatory, chemopreventative and antidiabetic properties. Several studies indicate the multiple effects of resveratrol on cellular function are due to its inhibition of class 1A phosphoinositide 3-kinase (PI3K) mediated signaling pathways, but it also activates AMP-activated protein kinase (AMPK). As sodium transport in the kidney via the Epithelial Sodium Channel (ENaC) is highly sensitive to changes in phosphoinositide signaling in the membrane and AMPK, we employed resveratrol to probe the relative effects of phosphatidylinositol species in the plasma membrane and AMPK activity and their impact on ENaC activity in mouse cortical collecting duct (mpkCCDc14) cells. Here we demonstrate that resveratrol acutely reduces amiloride-sensitive current in mpkCCDc14 cells. The time course and dose dependency of this inhibition paralleled depletion of the PI(3,4,5)P3 reporter (AKT-PH) in live-cell microscopy, indicating the early inhibition is likely mediated by resveratrol's known effects on PI3K activity. Additionally, resveratrol induces a late inhibitory effect (4-24 hours) that appears to be mediated via AMPK activation. Resveratrol treatment induces significant AMPK activation compared with vehicle controls after 4 h, which persists through 16 h. Knockdown of AMPK or treatment with the AMPK inhibitor Compound C reduced the late phase of current reduction but had no effect on the early inhibitory activity of resveratrol. Collectively, these data demonstrate that resveratrol inhibits ENaC activity by a dual effect: an early reduction in activity seen within 5 minutes related to depletion of membrane PIP3, and a sustained late (4-24 h) effect secondary to activation of AMPK.
format	article
author	Kelly M Weixel Allison Marciszyn Rodrigo Alzamora Hui Li Oliver Fischer Robert S Edinger Kenneth R Hallows John P Johnson
author_facet	Kelly M Weixel Allison Marciszyn Rodrigo Alzamora Hui Li Oliver Fischer Robert S Edinger Kenneth R Hallows John P Johnson
author_sort	Kelly M Weixel
title	Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
title_short	Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
title_full	Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
title_fullStr	Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
title_full_unstemmed	Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.
title_sort	resveratrol inhibits the epithelial sodium channel via phopshoinositides and amp-activated protein kinase in kidney collecting duct cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/aa5b842b25724128a8ddd3c7ded65dd4
work_keys_str_mv	AT kellymweixel resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT allisonmarciszyn resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT rodrigoalzamora resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT huili resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT oliverfischer resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT robertsedinger resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT kennethrhallows resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells AT johnpjohnson resveratrolinhibitstheepithelialsodiumchannelviaphopshoinositidesandampactivatedproteinkinaseinkidneycollectingductcells
_version_	1718421280655409152

Resveratrol inhibits the epithelial sodium channel via phopshoinositides and AMP-activated protein kinase in kidney collecting duct cells.

Ejemplares similares