Impact of polyunsaturated fatty acids on oxidized low density lipoprotein-induced U937 cell apoptosis

J Atheroscler Thromb. 2011;18(6):494-503. doi: 10.5551/jat.7062. Epub 2011 Feb 16.

Abstract

Aim: Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for their beneficial effects in preventing cardiovascular diseases (CVD). The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acidoxidized LDL (HOCl-oxLDL) in U937 cells.

Methods: We tested the effect of monocyte cell line U937 supplementation with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA) on the modulation of HOCl-oxLDL-induced apoptosis.

Results: First, we showed the incorporation of fatty acids in the cellular membrane in U937 cells. Then, we showed that both EPA and ARA exerted a pro-apoptotic effect through the intrinsic mitochondrial apoptotic pathway including the dissipation of mitochondrial membrane potential followed by cardiolipin depletion, the downstream activation of caspase-3 and the increase in DNA fragmentation. The pro-apoptotic effect of EPA or ARA was completely blocked in U937/Bcl-2 cells.

Conclusions: A new mechanism of dietary supplements in PUFA with likely consequences in apoptosis could be suggested through the mitochondrial pathway in monocytes.

MeSH terms

  • Apoptosis*
  • Arachidonic Acid / pharmacology*
  • Cardiolipins / metabolism
  • Caspase 3 / metabolism
  • Dietary Supplements
  • Docosahexaenoic Acids / pharmacology*
  • Eicosapentaenoic Acid / pharmacology*
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • U937 Cells

Substances

  • Cardiolipins
  • Fatty Acids
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Eicosapentaenoic Acid
  • Caspase 3