Dual metabolic pathways of 12-HETE in rat aortic smooth muscle cells.
12(S)-HETE, a major lipoxygenase-derived compound from arachidonic acid is incorporated and metabolized by vascular smooth muscle cells via beta-oxidation. We have now identified for the first time in this cell type 12(S)-HETE metabolites formed by a combination of reductase and oxidation pathways. HPLC and GC-MS analysis of time-course experiments allow us to characterize two different metabolic pathways: a direct peroxisomal beta-oxidation of 12(S)-HETE leading to the formation of 16:3 (8-OH) which accumulates first and a reduction of one of the conjugated double bonds of 12(S)-HETE giving the dihydro-intermediate 20:3(12-OH) that transiently accumulates before being converted itself by peroxisomal beta-oxidation to 16:2(8-OH). Taken together these results may suggest that the transient accumulation of 20:3(12-OH) through transcellular metabolism of 12(S)-HETE may represent a part of the modulatory effect of 12(S)-HETE on vascular function.
Lacape
G
G
Unite 8 de Cardiologie INSERM, Pessac, France.
Daret
D
D
Crockett
R
R
Rigaud
M
M
Larrue
J
J
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008055:Lipids / Q000302:isolation & purification; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D010743:Phospholipids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid