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Artículo

Ammonia detoxification via ureagenesis in rat hepatocytes involves mitochondrial aquaporin-8 channels

Soria, Leandro RaulIcon ; Marrone, JulietaIcon ; Calamita, Giuseppe; Marinelli, Raul AlbertoIcon
Fecha de publicación: 05/2013
Editorial: American Association for the Study of Liver Diseases
Revista: Hepatology (baltimore, Md.)
ISSN: 0270-9139
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Fisiología

Resumen

Hepatocyte mitochondrial ammonia detoxification via ureagenesis is critical for the prevention of hyperammonemia and hepatic encephalopathy. Aquaporin-8 (AQP8) channels facilitate the membrane transport of ammonia. Because AQP8 is expressed in hepatocyte inner mitochondrial membranes (IMMs), we studied whether mitochondrial AQP8 (mtAQP8) plays a role in ureagenesis from ammonia. Primary cultured rat hepatocytes were transfected with small interfering RNAs (siRNAs) targeting two different regions of the rat AQP8 molecule or with scrambled control siRNA. After 48 hours, the levels of mtAQP8 protein decreased by approximately 80% (P < 0.05) without affecting cell viability. mtAQP8 knockdown cells in the presence of ammonium chloride showed a decrease in ureagenesis of approximately 30% (P < 0.05). Glucagon strongly stimulated ureagenesis in control hepatocytes (+120%, P < 0.05) but induced no significant stimulation in mtAQP8 knockdown cells. Contrarily, mtAQP8 silencing induced no significant change in basal and glucagon-induced ureagenesis when glutamine or alanine was used as a source of nitrogen. Nuclear magnetic resonance studies using 15N-labeled ammonia confirmed that glucagon-induced 15N-labeled urea synthesis was markedly reduced in mtAQP8 knockdown hepatocytes (-90%, P < 0.05). In vivo studies in rats showed that under glucagon-induced ureagenesis, hepatic mtAQP8 protein expression was markedly up-regulated (+160%, P < 0.05). Moreover, transport studies in liver IMM vesicles showed that glucagon increased the diffusional permeability to the ammonia analog [(14) C]methylamine (+80%, P < 0.05).
Palabras clave: Urea Synthesis , Mitochondrial Ammonia Transport , Aqua-Ammoniaporin , Glucagon , Liver
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/6107
URL: http://dx.doi.org/ www.onlinelibrary.wiley.com/doi/10.1002/hep.26236
DOI: http://dx.doi.org/10.1002/hep.26236
DOI: http://dx.doi.org/ 10.1002/hep.26236
Colecciones
Articulos(IFISE)
Articulos de INST.DE FISIOLOGIA EXPERIMENTAL (I)
Citación
Soria, Leandro Raul; Marrone, Julieta; Calamita, Giuseppe; Marinelli, Raul Alberto; Ammonia detoxification via ureagenesis in rat hepatocytes involves mitochondrial aquaporin-8 channels; American Association for the Study of Liver Diseases; Hepatology (baltimore, Md.); 57; 5; 5-2013; 2061-2071
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