Alcohol dehydrogenase 3 contributes to the protection of liver from nonalcoholic steatohepatitis

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Maki GotoHozumi Motohashi

Abstract

Nutritional steatohepatitis is closely associated with dysregulation of lipid metabolism and oxidative stress control. ADH3 is a highly conserved bifunctional enzyme involved in formaldehyde detoxification and termination of nitric oxide signaling. Formaldehyde and nitric oxide are nonenzymatically conjugated with glutathione, which is regenerated after ADH3 metabolizes the conjugates. To clarify roles of ADH3 in nutritional liver diseases, we placed Adh3-null mice on a methionine- and choline-deficient (MCD) diet. The Adh3-null mice developed steatohepatitis more rapidly than wild-type mice, indicating that ADH3 protects liver from nutritional steatohepatitis. NRF2, which is a key regulator of cytoprotective genes against oxidative stress, was activated in the Adh3-null mice with liver damage. In the absence of NRF2, the Adh3 disruption caused severe steatohepatitis by the MCD diet feeding accompanied by significant decrease in glutathione, suggesting cooperative function between ADH3 and NRF2 in the maintenance of cellular glutathione level for cytoprotection. Conversely, with enhanced NRF2 activity, the Adh3 disruption did not cause steatohepatitis but induced steatosis, suggesting that perturbation of lipid metabolism in AD...Continue Reading

References

Feb 5, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gianfranco PaganoMario Rizzetto
Apr 2, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giulio MarchesiniMario Rizzetto
Oct 1, 2003·Nature Genetics·Nobunao WakabayashiMasayuki Yamamoto
Apr 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hozumi MotohashiMasayuki Yamamoto
May 28, 2005·Science·Loretta G QueJonathan S Stamler
Oct 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Martin KohlmeierSteven H Zeisel
Nov 2, 2005·Medicine and Science in Sports and Exercise·Jacques R PoortmansMarc Francaux
Nov 19, 2005·Biochemical and Biophysical Research Communications·Hiromi OkawaMasayuki Yamamoto
Jan 27, 2006·International Journal of Experimental Pathology·Quentin M Anstee, Robert D Goldin
Apr 11, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Janardan K Reddy, M Sambasiva Rao
Jun 2, 2006·Molecular and Cellular Biology·Hozumi MotohashiMasayuki Yamamoto
Mar 27, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jacqui M MarzecSteven R Kleeberger
Oct 2, 2007·Nature Chemical Biology·Tomohiro SawaTakaaki Akaike
Jan 8, 2008·The American Journal of Gastroenterology·Christine Carter-KentAriel E Feldstein
May 8, 2008·Current Opinion in Lipidology·Dennis E Vance
Jul 1, 2008·Archives of Biochemistry and Biophysics·Atsushi MaruyamaKen Itoh
Mar 28, 2009·FEBS Letters·Rima Obeid, Wolfgang Herrmann
Nov 17, 2009·Free Radical Biology & Medicine·Sudhir ChowdhryJohn D Hayes
Nov 21, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hirokazu SugimotoMasayuki Yamamoto
Mar 20, 2010·Metabolomics : Official Journal of the Metabolomic Society·Masahiro SugimotoMasaru Tomita
Mar 31, 2010·Toxicology and Applied Pharmacology·Yu-Kun Jennifer ZhangCurtis D Klaassen
Apr 8, 2010·Science Translational Medicine·Wei WeiLimin Liu
Apr 21, 2010·Molecular and Cellular Biology·Keiko TaguchiMasayuki Yamamoto
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael McMahonJohn D Hayes
Oct 27, 2010·Molecular and Cellular Biology·Hozumi MotohashiMasayuki Yamamoto
Mar 10, 2011·Nitric Oxide : Biology and Chemistry·Akira Uruno, Hozumi Motohashi
Nov 15, 2011·Nature Structural & Molecular Biology·Ivan V RosadoKetan J Patel
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Farideh BeigiJoshua M Hare
Feb 19, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Patrick Y SipsFumito Ichinose
Apr 11, 2013·Molecular and Cellular Biology·Takafumi SuzukiMasayuki Yamamoto
Nov 19, 2013·Biochemical and Biophysical Research Communications·Chi-Hui TangLimin Liu
Dec 20, 2013·BioFactors·Robin P da SilvaRené L Jacobs
Mar 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hyon-Seung YiWon-Il Jeong
Aug 19, 2014·European Journal of Heart Failure·Adele H GoodloeTimothy M Olson

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