TNFα induced up-regulation of Na+,K+,2Cl- cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity.
Sci Rep
; 7(1): 7938, 2017 08 11.
Article
em En
| MEDLINE
| ID: mdl-28801579
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Necrose Tumoral alfa
/
Hiperamonemia
/
Receptores Tipo I de Fatores de Necrose Tumoral
/
Receptores Tipo II do Fator de Necrose Tumoral
/
Membro 2 da Família 12 de Carreador de Soluto
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article