TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity

Abstract The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4 +. Cellular NH4 + uptake is accomplished mainly by the Na+,K+,2Cl− cotransporter....

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Autores principales:	Vitaly I. Pozdeev, Elisabeth Lang, Boris Görg, Hans J. Bidmon, Prashant V. Shinde, Gerald Kircheis, Diran Herebian, Klaus Pfeffer, Florian Lang, Dieter Häussinger, Karl S. Lang, Philipp A. Lang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca0324e4a21046279b31b2b97c7642c2
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spelling	oai:doaj.org-article:ca0324e4a21046279b31b2b97c7642c22021-12-02T11:52:25ZTNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity10.1038/s41598-017-07640-82045-2322https://doaj.org/article/ca0324e4a21046279b31b2b97c7642c22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07640-8https://doaj.org/toc/2045-2322Abstract The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4 +. Cellular NH4 + uptake is accomplished mainly by the Na+,K+,2Cl− cotransporter. Here we show that hepatic clearance of NH4 + is impaired in TNFα deficient as well as TNFR1&TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH4 +, TNFα deficient mice and TNFR1 deficient mice were protected against acute ammonia intoxication. While 54% of the wild-type mice and 60% of TNFR2 deficient mice survived an NH4 + load, virtually all TNFα deficient mice and TNFR1 deficient mice survived the treatment. Conversely, TNFα treatment of wild type mice sensitized the animals to the toxic effects of an NH4 + load. The protection of TNFα-deficient mice against an NH4 + load was paralleled by decreased cerebral expression of NKCC1. According to the present observations, inhibition of TNFα formation and/or NKCC1 may be strategies to favorably influence the clinical course of hepatic encephalopathy.Vitaly I. PozdeevElisabeth LangBoris GörgHans J. BidmonPrashant V. ShindeGerald KircheisDiran HerebianKlaus PfefferFlorian LangDieter HäussingerKarl S. LangPhilipp A. LangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vitaly I. Pozdeev Elisabeth Lang Boris Görg Hans J. Bidmon Prashant V. Shinde Gerald Kircheis Diran Herebian Klaus Pfeffer Florian Lang Dieter Häussinger Karl S. Lang Philipp A. Lang TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
description	Abstract The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4 +. Cellular NH4 + uptake is accomplished mainly by the Na+,K+,2Cl− cotransporter. Here we show that hepatic clearance of NH4 + is impaired in TNFα deficient as well as TNFR1&TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH4 +, TNFα deficient mice and TNFR1 deficient mice were protected against acute ammonia intoxication. While 54% of the wild-type mice and 60% of TNFR2 deficient mice survived an NH4 + load, virtually all TNFα deficient mice and TNFR1 deficient mice survived the treatment. Conversely, TNFα treatment of wild type mice sensitized the animals to the toxic effects of an NH4 + load. The protection of TNFα-deficient mice against an NH4 + load was paralleled by decreased cerebral expression of NKCC1. According to the present observations, inhibition of TNFα formation and/or NKCC1 may be strategies to favorably influence the clinical course of hepatic encephalopathy.
format	article
author	Vitaly I. Pozdeev Elisabeth Lang Boris Görg Hans J. Bidmon Prashant V. Shinde Gerald Kircheis Diran Herebian Klaus Pfeffer Florian Lang Dieter Häussinger Karl S. Lang Philipp A. Lang
author_facet	Vitaly I. Pozdeev Elisabeth Lang Boris Görg Hans J. Bidmon Prashant V. Shinde Gerald Kircheis Diran Herebian Klaus Pfeffer Florian Lang Dieter Häussinger Karl S. Lang Philipp A. Lang
author_sort	Vitaly I. Pozdeev
title	TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
title_short	TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
title_full	TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
title_fullStr	TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
title_full_unstemmed	TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity
title_sort	tnfα induced up-regulation of na+,k+,2cl− cotransporter nkcc1 in hepatic ammonia clearance and cerebral ammonia toxicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ca0324e4a21046279b31b2b97c7642c2
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TNFα induced up-regulation of Na+,K+,2Cl− cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity

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