Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

Abstract Ouabain (OUA) is a cardiac glycoside that binds to Na+,K+-ATPase (NKA), a conserved membrane protein that controls cell transmembrane ionic concentrations and requires ATP hydrolysis. At nM concentrations, OUA activates signaling pathways that are not related to its typical inhibitory effec...

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Autores principales:	Paula F. Kinoshita, Lidia M. Yshii, Ana Maria M. Orellana, Amanda G. Paixão, Andrea R. Vasconcelos, Larissa de Sá Lima, Elisa M. Kawamoto, Cristoforo Scavone
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1adf6f5253cc4c8bb05fb066494c48ed
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spelling	oai:doaj.org-article:1adf6f5253cc4c8bb05fb066494c48ed2021-12-02T16:06:57ZAlpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells10.1038/s41598-017-05075-92045-2322https://doaj.org/article/1adf6f5253cc4c8bb05fb066494c48ed2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05075-9https://doaj.org/toc/2045-2322Abstract Ouabain (OUA) is a cardiac glycoside that binds to Na+,K+-ATPase (NKA), a conserved membrane protein that controls cell transmembrane ionic concentrations and requires ATP hydrolysis. At nM concentrations, OUA activates signaling pathways that are not related to its typical inhibitory effect on the NKA pump. Activation of these signaling pathways protects against some types of injury of the kidneys and central nervous system. There are 4 isoforms of the alpha subunit of NKA, which are differentially distributed across tissues and may have different physiological roles. Glial cells are important regulators of injury and inflammation in the brain and express the α1 and α2 NKA isoforms. This study investigated the role of α2 NKA in OUA modulation of the neuroinflammatory response induced by lipopolysaccharide (LPS) in mouse primary glial cell cultures. LPS treatment increased lactate dehydrogenase release, while OUA did not decrease cell viability and blocked LPS-induced NF-κB activation. Silencing α2 NKA prevented ERK and NF-κB activation by LPS. α2 NKA also regulates TNF-α and IL-1β levels. The data reported here indicate a significant role of α2 NKA in regulating central LPS effects, with implications in the associated neuroinflammatory processes.Paula F. KinoshitaLidia M. YshiiAna Maria M. OrellanaAmanda G. PaixãoAndrea R. VasconcelosLarissa de Sá LimaElisa M. KawamotoCristoforo ScavoneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paula F. Kinoshita Lidia M. Yshii Ana Maria M. Orellana Amanda G. Paixão Andrea R. Vasconcelos Larissa de Sá Lima Elisa M. Kawamoto Cristoforo Scavone Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
description	Abstract Ouabain (OUA) is a cardiac glycoside that binds to Na+,K+-ATPase (NKA), a conserved membrane protein that controls cell transmembrane ionic concentrations and requires ATP hydrolysis. At nM concentrations, OUA activates signaling pathways that are not related to its typical inhibitory effect on the NKA pump. Activation of these signaling pathways protects against some types of injury of the kidneys and central nervous system. There are 4 isoforms of the alpha subunit of NKA, which are differentially distributed across tissues and may have different physiological roles. Glial cells are important regulators of injury and inflammation in the brain and express the α1 and α2 NKA isoforms. This study investigated the role of α2 NKA in OUA modulation of the neuroinflammatory response induced by lipopolysaccharide (LPS) in mouse primary glial cell cultures. LPS treatment increased lactate dehydrogenase release, while OUA did not decrease cell viability and blocked LPS-induced NF-κB activation. Silencing α2 NKA prevented ERK and NF-κB activation by LPS. α2 NKA also regulates TNF-α and IL-1β levels. The data reported here indicate a significant role of α2 NKA in regulating central LPS effects, with implications in the associated neuroinflammatory processes.
format	article
author	Paula F. Kinoshita Lidia M. Yshii Ana Maria M. Orellana Amanda G. Paixão Andrea R. Vasconcelos Larissa de Sá Lima Elisa M. Kawamoto Cristoforo Scavone
author_facet	Paula F. Kinoshita Lidia M. Yshii Ana Maria M. Orellana Amanda G. Paixão Andrea R. Vasconcelos Larissa de Sá Lima Elisa M. Kawamoto Cristoforo Scavone
author_sort	Paula F. Kinoshita
title	Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
title_short	Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
title_full	Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
title_fullStr	Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
title_full_unstemmed	Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells
title_sort	alpha 2 na+,k+-atpase silencing induces loss of inflammatory response and ouabain protection in glial cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1adf6f5253cc4c8bb05fb066494c48ed
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Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells

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