Effects of short-chain acyl-CoA dehydrogenase on cardiomyocyte apoptosis

J Cell Mol Med. 2016 Jul;20(7):1381-91. doi: 10.1111/jcmm.12828. Epub 2016 Mar 17.

Abstract

Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid β-oxidation, plays an important role in cardiac hypertrophy. However, its effect on the cardiomyocyte apoptosis remains unknown. We aimed to determine the role of SCAD in tert-butyl hydroperoxide (tBHP)-induced cardiomyocyte apoptosis. The mRNA and protein expression of SCAD were significantly down-regulated in the cardiomyocyte apoptosis model. Inhibition of SCAD with siRNA-1186 significantly decreased SCAD expression, enzyme activity and ATP content, but obviously increased the content of free fatty acids. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP, such as the increase in cell apoptotic rate, the activation of caspase3 and the decrease in the Bcl-2/Bax ratio, which showed that SCAD may play an important role in primary cardiomyocyte apoptosis. The changes of phosphonate AMP-activated protein kinase α (p-AMPKα) and Peroxisome proliferator-activated receptor α (PPARα) in cardiomyocyte apoptosis were consistent with that of SCAD. Furthermore, PPARα activator fenofibrate and AMPKα activator AICAR treatment significantly increased the expression of SCAD and inhibited cardiomyocyte apoptosis. In conclusion, for the first time our findings directly demonstrated that SCAD may be as a new target to prevent cardiomyocyte apoptosis through the AMPK/PPARα/SCAD signal pathways.

Keywords: AMP-activated protein kinase; cardiomyocyte apoptosis; energy metabolism•; peroxisome proliferator-activated receptor α; short-chain acyl-CoA dehydrogenase; tert-butyl hydroperoxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Animals, Newborn
  • Apoptosis* / drug effects
  • Butyryl-CoA Dehydrogenase / metabolism*
  • Cardiotonic Agents / pharmacology
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Fenofibrate / pharmacology
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / enzymology*
  • PPAR alpha / metabolism
  • RNA, Small Interfering / metabolism
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Ribonucleotides / pharmacology
  • tert-Butylhydroperoxide / pharmacology

Substances

  • Cardiotonic Agents
  • PPAR alpha
  • RNA, Small Interfering
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • tert-Butylhydroperoxide
  • Butyryl-CoA Dehydrogenase
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Fenofibrate