Docosahexaenoic Acid Affects Endothelial Nitric Oxide Synthase in Caveolae

Arch Biochem Biophys. 2007 Oct 15;466(2):250-9. doi: 10.1016/j.abb.2007.06.023. Epub 2007 Jun 29.

Abstract

n-3 Polyunsaturated fatty acids are assumed to play an important role in the prevention and treatment of atherosclerosis. Endothelial nitric-oxide synthase (eNOS) is responsible for cardiovascular homeostasis involving in regulation of vascular function, and the subcellular localization is critical for its activation. Here we determined the effect of docosahexaenoic acid (DHA, 22:6 n-3) on distribution of eNOS and its activity. DHA treatment markedly altered lipid environment of caveolae microdomains, which was coincided with selective displacement of caveolin-1 and eNOS from caveolae. Akt was not detected in caveolae fractions and CaM was distributed in both of caveolin-1-enriched membranes and non-caveolar fractions, whose distribution was unaffected by DHA. These data demonstrated for the first time that DHA altered caveolae microenvironment not only by modifying membrane lipid composition, but also by changing distribution of major structural proteins. DHA-induced alterations in caveolae lipid/protein environment may be an important mechanism in the development of pathogenesis of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin / metabolism
  • Caveolae / enzymology*
  • Caveolin 1 / metabolism
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Docosahexaenoic Acids / pharmacology*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Fatty Acids / metabolism
  • Humans
  • Nitric Oxide Synthase Type III / metabolism*
  • Phospholipids / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Calmodulin
  • Caveolin 1
  • Fatty Acids
  • Phospholipids
  • Docosahexaenoic Acids
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt