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Hyperammonemia enhances the function and expression of P-glycoprotein and Mrp2 at the blood-brain barrier through NF-κB.
- Source :
-
Journal of Neurochemistry . Dec2014, Vol. 131 Issue 6, p791-802. 12p. - Publication Year :
- 2014
-
Abstract
- Ammonia is considered to be the main neurotoxin responsible for hepatic encephalopathy resulting from liver failure. Liver failure has been reported to alter expression and activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) at the blood-brain barrier (BBB). The aim of this study was to investigate whether ammonia is involved in abnormalities of expression and activity of P-gp and Mrp2 at the BBB. Hyperammonemic rats were developed by an intraperitoneal injection of ammonium acetate (NH4Ac, 4.5 mmol/kg). Results showed that Mrp2 function markedly increased in cortex and hippocampus of rats at 6 h following NH4Ac administration. Significant increase in function of P-gp was observed in hippocampus of rats. Meanwhile, such alterations were in line with the increase in mRNA and protein levels of P-gp and Mrp2. Significant increase in levels of nuclear amount of nuclear factor-κB (NF-κB) p65 was also observed. Primarily cultured rat brain microvessel endothelial cells ( rBMECs) were used for in vitro study. Data indicated that 24 h exposure to ammonia significantly increased function and expression of P-gp and Mrp2 in rBMECs, accompanied with activation of NF-κB. Furthermore, such alterations induced by ammonia were reversed by NF-κB inhibitor. In conclusion, this study demonstrates that hyperammonemia increases the function and expression of P-gp and Mrp2 at the BBB via activating NF-κB pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 131
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 99839495
- Full Text :
- https://doi.org/10.1111/jnc.12944