title: Lipopolysaccharide impairs hepatocyte ureagenesis from ammonia: involvement of mitochondrial aquaporin-8.
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.
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Leandro R
authors.initials: LR
authors.lastname: Soria
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Marrone
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Molinas
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina; Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Guillermo L
authors.initials: GL
authors.lastname: Lehmann
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari Aldo Moro, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calamita
authors.affiliation: Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina. Electronic address: rmarinel@unr.edu.ar.
authors.forename: Raúl A
authors.initials: RA
authors.lastname: Marinelli
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D005934:Glucagon / Q000502:physiology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008744:Methylamines / Q000378:metabolism; D008930:Mitochondria, Liver / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D008070:Lipopolysaccharides; D008744:Methylamines; C108330:aquaporin 8; D000641:Ammonia; D014508:Urea; D005934:Glucagon; C027451:methylamine
keywords: Aquaporin-8; Llipopolysaccharide; Mitochondrial ammonia transport; Urea synthesis; hepatocyte