Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS

Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H656-64. doi: 10.1152/ajpheart.00726.2001.

Abstract

The saturated fatty acid palmitate induces apoptosis in neonatal rat cardiomyocytes. This apoptosis is associated with early mitochondrial release of cytochrome c and a subsequent loss of mitochondrial membrane potential. Recent reports implicate a role for reactive oxygen species (ROS) in palmitate-induced apoptosis. We studied the role of ROS in palmitate-induced apoptosis in the neonatal rat cardiomyocyte and report no evidence of ROS involvement. ROS production, nitric oxide production, and nuclear factor-kappaB activation were not increased above those observed using the nonapoptotic fatty acid oleate. Indeed, the production of ROS was significantly higher in cells treated with oleate. Furthermore, the presence of antioxidants and ROS scavengers did not attenuate the induction of apoptosis by palmitate. Variations in the fatty acid-to-albumin ratio from 2:1 to 7:1 had no effect on the absence of ROS production or on the extent of apoptosis. No evidence was found for an increase in oxidative protein modification in palmitate-treated cells. Our results lead us to conclude that oxidative stress does not play a role in palmitate-induced apoptosis.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / metabolism
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Ditiocarb / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Fluoresceins
  • Hydrogen Peroxide / metabolism
  • Mitochondria / metabolism
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / metabolism*
  • Myocardium / cytology*
  • Myocardium / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Oleic Acid / pharmacology
  • Oxidation-Reduction
  • Palmitic Acid / pharmacology*
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Chelating Agents
  • Enzyme Inhibitors
  • Fluoresceins
  • NF-kappa B
  • Proteins
  • Reactive Oxygen Species
  • diacetyldichlorofluorescein
  • Oleic Acid
  • Palmitic Acid
  • Nitric Oxide
  • Ditiocarb
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • Casp3 protein, rat
  • Caspase 3
  • Caspases