Metabolism of 5-hydroxy-6,8,11,14-eicosatetraenoic acid by human endothelial cells

• Published in: Biochemical and biophysical research communications 2006-11, Vol.350 (1), p.151-156
• Main Authors: Erlemann, Karl-Rudolf, Cossette, Chantal, Gravel, Sylvie, Stamatiou, Panagiota B., Lee, Gue-Jae, Rokach, Joshua, Powell, William S.
• Format: Article
• Language: English
• Subjects: 5-HETE; 5-Hydroxyeicosanoid dehydrogenase; 5-Lipoxygenase; 5-Oxo-ETE; Arachidonic Acids - biosynthesis; Cells, Cultured; Eicosanoids; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Glutathione; Glutathione - metabolism; Humans; Hydrogen Peroxide - pharmacology; Hydroxyeicosatetraenoic Acids - metabolism; Inflammation; NADP; Oxidation-Reduction; Oxidative Stress; Pentose Phosphate Pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.09.011

There is increasing evidence that proinflammatory products of the 5-lipoxygenase pathway play an important role in cardiovascular disease. In the present study, we found that human endothelial cells rapidly oxidize the 5-lipoxygenase product 5 S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent chemoattractant for myeloid cells. 5-Oxo-ETE synthesis is strongly stimulated by oxidative stress. This effect is enhanced following inhibition of the pentose phosphate pathway with dehydroepiandrosterone and is mimicked by diamide, which oxidizes intracellular GSH to GSSG. Conversely, it is blocked by depletion of intracellular GSH/GSSG. The kinetics of H 2O 2-induced 5-oxo-ETE synthesis by endothelial cells correlate well with changes in the intracellular levels of GSSG and NADP +. These results suggest that exposure of the endothelium to oxidative stress and inflammation could result in the synthesis of 5-oxo-ETE, which could then induce the infiltration of inflammatory cells into the tissue.