Acetylation-dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol-induced eNOS activation

FEBS Lett. 2012 Jan 20;586(2):137-42. doi: 10.1016/j.febslet.2011.11.031. Epub 2011 Dec 7.

Abstract

Moderate alcohol consumption has beneficial effects on endothelial nitric-oxide synthase (eNOS) activation, which can engender an array of anti-atherogenic actions. Here we show that in human aortic endothelial cells (HAECs), rapid activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) mediates ethanol-induced eNOS activation by preventing reactive oxygen species (ROS) accumulation. Furthermore, activation of ALDH2 by ethanol is due to its hyperacetylation by SIRT3 inactivation. These data suggest that ethanol-induced eNOS activation in HAECs may be dependent on ALDH2 hyperacetylation by SIRT3 inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Ethanol / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / genetics
  • RNA, Small Interfering / pharmacology
  • Reactive Oxygen Species / metabolism
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*
  • Transfection

Substances

  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Ethanol
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Acetyltransferases
  • SIRT3 protein, human
  • Sirtuin 3