Activation of aldehyde dehydrogenase 2 (ALDH2) confers cardioprotection in protein kinase C epsilon (PKCvarepsilon) knockout mice.

Journal of Molecular and Cellular Cardiology
Grant R BudasD Mochly-Rosen

Abstract

Acute administration of ethanol can reduce cardiac ischemia/reperfusion injury. Previous studies demonstrated that the acute cytoprotective effect of ethanol on the myocardium is mediated by protein kinase C epsilon (PKCvarepsilon). We recently identified aldehyde dehydrogenase 2 (ALDH2) as a PKCvarepsilon substrate, whose activation is necessary and sufficient to confer cardioprotection in vivo. ALDH2 metabolizes cytotoxic reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), which accumulate during cardiac ischemia/reperfusion. Here, we used a combination of PKCvarepsilon knockout mice and a direct activator of ALDH2, Alda-44, to further investigate the interplay between PKCvarepsilon and ALDH2 in cardioprotection. We report that ethanol preconditioning requires PKCvarepsilon, whereas direct activation of ALDH2 reduces infarct size in both wild type and PKCvarepsilon knockout hearts. Our data suggest that ALDH2 is downstream of PKCvarepsilon in ethanol preconditioning and that direct activation of ALDH2 can circumvent the requirement of PKCvarepsilon to induce cytoprotection. We also report that in addition to ALDH2 activation, Alda-44 prevents 4-HNE induced inactivation of ALDH2 by reducing the formation of 4-HNE-ALDH2 pr...Continue Reading

References

Nov 1, 1992·Journal of Molecular and Cellular Cardiology·S W WernsB R Lucchesi
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·K Uchida, E R Stadtman
Jan 1, 1991·Free Radical Biology & Medicine·H EsterbauerH Zollner
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·R BolliP B McCay
Jan 5, 1996·Biochemical and Biophysical Research Communications·R J Knight, D B Buxton
Mar 15, 1996·The Journal of Biological Chemistry·B S KristalB P Yu
Jan 1, 1996·Free Radical Biology & Medicine·W G SiemsF J van Kuijk
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·M MiyamaeV M Figueredo
Aug 8, 1997·The Journal of Biological Chemistry·T YinJ Whelan
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·M MiyamaeV M Figueredo
Dec 3, 1998·The Journal of Clinical Investigation·M ParolaM U Dianzani
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·C H ChenD Mochly-Rosen
Jan 1, 1996·Journal of Thrombosis and Thrombolysis·S D BellowsR A Kloner
Jan 13, 2001·Chemico-biological Interactions·V VasiliouD R Petersen
Feb 22, 2001·Journal of Molecular and Cellular Cardiology·C Chen, D Mochly-Rosen
Jan 12, 2002·The Journal of Biological Chemistry·Hiroki AokiSeigo Izumo
Jun 21, 2002·Annals of the New York Academy of Sciences·Maike KrenzJames M Downey
Sep 1, 2004·Free Radical Biology & Medicine·Dennis R Petersen, Jonathan A Doorn
Aug 17, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zhiqiang ChenJonathan S Stamler
Jan 18, 2006·Chemical Research in Toxicology·Jonathan A DoornDennis R Petersen
Mar 15, 2006·Archives of Biochemistry and Biophysics·Luc FaroutBertrand Friguet
Sep 12, 2007·Circulation·Robert A Kloner, Shereif H Rezkalla
Jan 22, 2008·Journal of the American College of Cardiology·Giampaolo NiccoliFilippo Crea
Sep 13, 2008·Science·Che-Hong ChenDaria Mochly-Rosen
Sep 20, 2008·The Biochemical Journal·Bradford G HillSanjay Srivastava
May 13, 2009·The Biochemical Journal·Joydip DasSimon J Slater

❮ Previous
Next ❯

Citations

Jun 19, 2010·Cardiovascular Research·Che-Hong ChenDaria Mochly-Rosen
Jul 27, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Douglas A StollerElizabeth M McNally
Oct 25, 2011·The Journal of Biological Chemistry·May KhannaThomas D Hurley
Mar 26, 2013·Basic Research in Cardiology·Hussain ContractorRajesh K Kharbanda
Oct 10, 2014·Journal of Neural Transmission·Edna Grünblatt, Peter Riederer
Dec 24, 2014·BMC Genomics·Marine GueugneauDaniel Béchet
Nov 26, 2010·Free Radical Biology & Medicine·Matthew J PickloMark R Hoffmann
Nov 2, 2011·Journal of Molecular and Cellular Cardiology·Maike Krenz, Ronald J Korthuis
Mar 3, 2017·Biochemical and Biophysical Research Communications·Qiuping ZhangMengwei Sun
Mar 27, 2018·Cardiovascular Research·Cintia Bagne UetaJulio Cesar Batista Ferreira
Jan 3, 2014·Physiological Reviews·Che-Hong ChenDaria Mochly-Rosen
Nov 14, 2014·British Journal of Pharmacology·S-B OngD J Hausenloy
Nov 7, 2019·Alcoholism, Clinical and Experimental Research·Fanrong Yao, Abdel A Abdel-Rahman
Oct 31, 2014·Proteins·Javier A Belmont-DíazJosé S Rodríguez-Zavala
Mar 29, 2014·Chembiochem : a European Journal of Chemical Biology·Bibek ParajuliThomas D Hurley
Feb 4, 2011·American Journal of Physiology. Renal Physiology·Grazyna NowakAllen M Samarel
Jul 25, 2018·World Journal of Gastroenterology : WJG·Arnau Panisello-RosellóJoan Roselló-Catafau
Feb 13, 2018·Expert Opinion on Therapeutic Targets·Thomas Münzel, Andreas Daiber
Oct 17, 2017·Frontiers in Cell and Developmental Biology·Jan Dudek
Feb 23, 2021·European Journal of Pharmacology·Leonardo da Cunha Menezes SouzaDaisy Maria Fávero Salvadori

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.