Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes

Vishal R. Mali, Mandar Deshpande, Guodong Pan, Rajarajan Amirthalingam Thandavarayan, Suresh S. Palaniyandi

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)+-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalCellular Signalling
Volume28
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • 4-Hydroxy-2-nonenal
  • Aldehyde dehydrogenase-2
  • Cell death
  • H9C2 cardiomyocytes
  • Mitochondrial respiration
  • Mitochondrial respiratory reserve capacity

ASJC Scopus subject areas

  • Cell Biology

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