title: Effects of dietary vitamin E on the biosynthesis of 5-lipoxygenase products by rat polymorphonuclear leukocytes (PMNL).
abstract: Activation of polymorphonuclear neutrophils (PMNL) leads to the release of arachidonate from cellular phospholipids via a phospholipase A2, and conversion of products of the 5-lipoxygenase pathway. Evidence to date indicates the dietary vitamin E ((R,R,R)-alpha-tocopherol) can influence both cyclooxygenase and phospholipase A2 activities and that the effect of this vitamin is cell/tissue specific. The present study was undertaken in order to examine the effects of varying dietary tocopherol on PMNL tocopherol content and 5-lipoxygenase product profile using the ionophore A23187 as stimulant in the presence and absence of exogenous arachidonate. Feeding semi-purified diets containing 0, 30 or 3000 ppm of (R,R,R)-alpha-tocopherol acetate to weanling rats for 17 weeks resulted in a dose-related enrichment of PMNL tocopherol. Stimulation of PMNL elicited a significant and rapid loss of tocopherol. When PMNL were stimulated with A23187 alone, the synthesis of 5-HETE, LTB4 and 19-hydroxy-LTB4 was decreased in proportion to increasing dietary tocopherol concentrations. However, when exogenous arachidonate was provided with A23187, intermediate amounts of dietary tocopherol (30 ppm) still suppressed the formation of 5-lipoxygenase products, but high doses (3000 ppm) did not have any additional inhibitory effect. This differential response to high concentrations of vitamin E in the presence and absence of exogenous arachidonate highly suggest that at these concentrations, tocopherol may act principally at the level of substrate release whereas at lower concentrations, 5-lipoxygenase is inhibited. Data from this study demonstrated that attenuation of the formation of 5-lipoxygenase products in PMNL can be achieved by dietary vitamin E enrichment.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Chan
authors.forename: K
authors.initials: K
authors.lastname: Tran
authors.forename: D D
authors.initials: DD
authors.lastname: Pyke
authors.forename: W S
authors.initials: WS
authors.lastname: Powell
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood*; D001091:Arachidonate Lipoxygenases / Q000097:blood*; D001095:Arachidonic Acids / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D004032:Diet; D004789:Enzyme Activation; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
chemical_list: D001095:Arachidonic Acids; D014810:Vitamin E; D000001:Calcimycin; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D024502:alpha-Tocopherol; D024505:Tocopherols