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Lipopolysaccharide impairs hepatocyte ureagenesis from ammonia: Involvement of mitochondrial aquaporin‐8
Author(s) -
Soria Leandro R.,
Marrone Julieta,
Molinas Sara M.,
Lehmann Guillermo L.,
Calamita Giuseppe,
Marinelli Raúl A.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.03.012
Subject(s) - hepatocyte , ammonia , urea , chemistry , lipopolysaccharide , metabolism , biochemistry , mitochondrion , biology , endocrinology , in vitro
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 15 N‐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.