Metabolism of 5-hydroxy-6,8,11,14-eicosatetraenoic acid by human endothelial cells.
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 5S-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 H2O2-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.
Erlemann
Karl-Rudolf
KR
Meakins-Christie Laboratories, Department of Medicine, McGill University, 3626 St. Urbain Street, Montreal, Que., Canada H2X 2P2.
Cossette
Chantal
C
Gravel
Sylvie
S
Stamatiou
Panagiota B
PB
Lee
Gue-Jae
GJ
Rokach
Joshua
J
Powell
William S
WS
D001095:Arachidonic Acids / Q000096:biosynthesis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D006861:Hydrogen Peroxide; D005978:Glutathione