Referenced in: none

Automatically associated channels: Kv10.1

Title: Lipopolysaccharide impairs hepatocyte ureagenesis from ammonia: involvement of mitochondrial aquaporin-8.

Authors: Leandro R Soria, Julieta Marrone, Sara M Molinas, Guillermo L Lehmann, Giuseppe Calamita, Raúl A Marinelli

Journal, date & volume: FEBS Lett., 2014 May 2 , 588, 1686-91

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24642373

Abstract
We recently reported that hepatocyte mitochondrial aquaporin-8 (mtAQP8) channels facilitate the uptake of ammonia and its metabolism into urea. Here we studied the effect of bacterial lipopolysaccharides (LPS) on ammonia-derived ureagenesis. In LPS-treated rats, hepatic mtAQP8 protein expression and diffusional ammonia permeability (measured utilizing ammonia analogues) of liver inner mitochondrial membranes were downregulated. NMR studies using 15N-labeled ammonia indicated that basal and glucagon-induced ureagenesis from ammonia were significantly reduced in hepatocytes from LPS-treated rats. Our data suggest that hepatocyte mtAQP8-mediated ammonia removal via ureagenesis is impaired by LPS, a mechanism potentially relevant to the molecular pathogenesis of defective hepatic ammonia detoxification in sepsis.