Inhibition of glutamine transport into mitochondria protects astrocytes from ammonia toxicity

V B R PichiliM D Norenberg


Hepatic encephalopathy (HE) is a major neurological complication that occurs in the setting of severe liver failure. Ammonia is a key neurotoxin implicated in this condition, and astrocytes are the principal neural cells histopathologically and functionally affected. Although the mechanism by which ammonia causes astrocyte dysfunction is incompletely understood, glutamine, a by-product of ammonia metabolism, has been strongly implicated in many of the deleterious effects of ammonia on astrocytes. Inhibiting mitochondrial glutamine hydrolysis in astrocytes mitigates many of the toxic effects of ammonia, suggesting the involvement of mitochondrial glutamine metabolism in the mechanism of ammonia neurotoxicity. To determine whether mitochondriaare indeed the organelle where glutamine exerts its toxic effects, we examined the effect of L-histidine, an inhibitor of mitochondrial glutamine transport, on ammonia-mediated astrocyte defects. Treatment of cultured astrocytes with L-histidine completely blocked or significantly attenuated ammonia-induced reactive oxygen species production, cell swelling, mitochondrial permeability transition, and loss of ATP. These findings implicate mitochondrial glutamine transport in the mechanism of a...Continue Reading


Sep 10, 1976·European Journal of Clinical Investigation·C O RecordR Williams
Feb 2, 1979·Brain Research·M D Norenberg, A Martinez-Hernandez
Jan 1, 1992·Canadian Journal of Physiology and Pharmacology·J E Olson, J A Evers
Mar 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M SwainA T Blei
Jul 1, 1991·Neurochemical Research·M D NorenbergJ T Neary
Jun 1, 1991·Digestive Diseases and Sciences·L Capocaccia, M Angelico
Jun 1, 1991·Transplantation Proceedings·R H Wiesner
Nov 1, 1988·Revue française de transfusion et immuno-hématologie·A BismuthC Serre
Sep 1, 1988·Journal of Neurochemistry·M YudkoffD Pleasure
Aug 1, 1986·Journal of Cellular Physiology·J E OlsonD Fleischhacker
Jun 1, 1971·Archives of Internal Medicine·B T HouraniT B Reynolds
Sep 1, 1969·The Biochemical Journal·D Shepherd, P B Garland
Jul 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J R McConnellB W Shaw
Jun 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A T BleiR F Butterworth
Mar 1, 1993·Journal of Neurochemistry·R A HawkinsM R De Joseph
Nov 5, 1997·Journal of Neurology, Neurosurgery, and Psychiatry·E A Jones, K Weissenborn
Jan 23, 1999·BioFactors·P BernardiL Scorrano
Mar 3, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J O ClemmesenP Ott
Feb 12, 1999·Metabolic Brain Disease·M D Norenberg
Apr 24, 1999·Neurochemical Research·B RobergE Kvamme
Nov 7, 1999·Journal of Hepatology·A T Blei, F S Larsen
Jan 5, 2000·Journal of the Neurological Sciences·J Albrecht, E A Jones
Mar 10, 2001·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·T Obata, Y Yamanaka
Oct 10, 2001·Journal of Neuroscience Research·C R MurthyM D Norenberg
Dec 1, 2001·Metabolic Brain Disease·K V Rao, M D Norenberg
Dec 18, 2001·Journal of Neuroscience Research·G BaiM D Norenberg
May 1, 2002·The Journal of Cell Biology·Farrukh A ChaudhryRobert H Edwards
May 9, 2002·Medicine·Saul W Brusilow
Feb 27, 2003·Metabolic Brain Disease·Roger F Butterworth
May 14, 2003·Neurochemistry International·K V Rama RaoM D Norenberg
Jun 26, 2003·Metabolic Brain Disease·K V Rama RaoD M Norenberg

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Oct 14, 2008·The Journal of Biological Chemistry·Arumugam R JayakumarMichael D Norenberg
Jan 21, 2014·Translational Stroke Research·A R JayakumarM D Norenberg
May 18, 2011·The International Journal of Neuroscience·E V StelmashookL G Khaspekov
Oct 20, 2010·Drug and Chemical Toxicology·Timur V SchäferVladimir L Rejniuk
Aug 20, 2010·Journal of Neuropathology and Experimental Neurology·Kakulavarapu V Rama RaoMichael D Norenberg
Jan 31, 2012·Neurochemistry International·Kakulavarapu V Rama RaoMichael D Norenberg
Oct 13, 2011·Neurochemistry International·Kakulavarapu V Rama Rao, Michael D Norenberg
Jan 16, 2010·The American Journal of Pathology·Kakulavarapu V Rama RaoMichael D Norenberg
Aug 26, 2009·The International Journal of Biochemistry & Cell Biology·José M MatésJavier Márquez
Aug 19, 2008·Seminars in Pediatric Neurology·Gregory M Enns
Apr 22, 2009·Journal of Neuroscience Research·Pichili V B ReddyMichael D Norenberg
May 7, 2009·Journal of Neurochemistry·Sven Gottschalk, Claudia Zwingmann
Jul 13, 2011·Journal of Neuroscience Research·Veronica M AlvarezMichael D Norenberg
Jul 27, 2010·Biochemical Pharmacology·Jan AlbrechtMichael D Norenberg
Nov 13, 2012·Neurochemistry International·Marta Skowrońska, Jan Albrecht
Apr 14, 2015·Mayo Clinic Proceedings·Elliot B TapperVilas R Patwardhan
Jul 29, 2016·Neurochemical Research·Simo S OjaEsa R Korpi
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