Direct molecular and spectroscopic evidence for increased ammonia removal capacity of skeletal muscle in acute liver failure

Journal of Hepatology
Nicolas ChatauretRoger F Butterworth

Abstract

It has been proposed that, in acute liver failure, skeletal muscle adapts to become the principle organ responsible for removal of blood-borne ammonia by increasing glutamine synthesis, a reaction that is catalyzed by the cytosolic ATP-dependent enzyme glutamine synthetase. To address this issue, glutamine synthetase expression and activities were measured in skeletal muscle of rats with acute liver failure resulting from hepatic devascularization. Glutamine synthetase protein and gene expression were investigated using immunoblotting and semi-quantitative RT-PCR analysis. Glutamine synthetase activity and glutamine de novo synthesis were measured using, respectively, a standard enzymatic assay and [13C]-nuclear magnetic resonance spectroscopy. Glutamine synthetase protein (but not gene) expression and enzyme activities were significantly up-regulated leading to increased de novo synthesis of glutamine and increased skeletal muscle capacity for ammonia removal in acute liver failure. In contrast to skeletal muscle, expression and activities of glutamine synthetase in the brain were significantly decreased. These findings demonstrate that skeletal muscle adapts, through a rapid induction of glutamine synthetase, to increase its ...Continue Reading

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Citations

Nov 17, 2007·Journal of Gastroenterology and Hepatology·Peter SörösManfred J Müller
Jan 5, 2008·Neurological Research·Javier Vaquero, Roger F Butterworth
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jia QiuSrinivasan Dasarathy
Mar 3, 2012·Neurochemistry International·Paul DesjardinsRoger F Butterworth
Jul 20, 2010·Lancet·William BernalJulia Wendon
Jan 16, 2010·The American Journal of Pathology·Kakulavarapu V Rama RaoMichael D Norenberg
Apr 22, 2015·Advanced Drug Delivery Reviews·Simon Matoori, Jean-Christophe Leroux
Oct 25, 2016·The Journal of Physiology·Gangarao DavuluriSrinivasan Dasarathy
Feb 6, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Renuka ManiRamakrishnan Arumugam
Jul 5, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Omar CauliVicente Felipo
Jul 31, 2014·American Journal of Physiology. Endocrinology and Metabolism·Yasutomi KameiYoshihiro Ogawa
Dec 5, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·John McDanielSrinivasan Dasarathy
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Apr 1, 2021·Minerva Gastroenterology·Salvatore S SciarroneMarco Senzolo
Oct 25, 2020·Journal of Hepatology·Christopher F RoseRajiv Jalan

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