title: Effect of vitamin E on oxysterol- and fatty acid hydroperoxide-induced changes of repair and permeability properties of cultured endothelial cell monolayers.
abstract: Oxidation products of fatty acids (fatty acid hydroperoxides) or of cholesterol (oxysterols) may be atherogenic by being injurious to the vascular endothelium. Vitamin E may protect cells against such injury by acting as an antioxidant and by regulating cell growth and/or repair. As indices of proliferation and growth/repair, synthesis of DNA [3H]thymidine incorporation) and protein ([3H]leucine incorporation), as affected by exposure to linoleic acid hydroperoxide (18:2-OOH), cholestan-3 beta, 5 alpha, 6 beta-triol (Triol), and/or alpha-tocopherol, was determined in confluent vascular endothelial cell cultures. Cell injury was assessed by measuring the passage of albumin through a cultured endothelial monolayer. Exposure to either Triol or 18:2-OOH significantly increased the rate of albumin transfer across endothelial monolayers. Prior enrichment with vitamin E protected endothelial cells from injury by 18:2-OOH but not Triol. Cell exposure to 25 microM vitamin E increased DNA synthesis compared with control cultures. DNA synthesis was also elevated in 18:2-OOH exposed cells, whereas Triol had no effect on cell replication. Prior cell exposure to vitamin E prevented the marked increase in DNA synthesis seen with 18:2-OOH. Protein synthesis was increased by 18:2-OOH, but not by Triol or vitamin E treatment. These results show that 1) both Triol and 18:2-OOH are cytotoxic, 2) vitamin E stimulates cell proliferation, 3) vitamin E protects cells against 18:2-OOH- but not Triol-induced cell injury (i.e., increased permeability to albumin), and 4) endothelial cell damage initiated by 18:2-OOH, but not Triol, stimulates synthesis of DNA and protein in an attempt to divide and repair the injury.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Nutrition and Food Science, University of Kentucky, Lexington.
authors.forename: B
authors.initials: B
authors.lastname: Hennig
authors.forename: G A
authors.initials: GA
authors.lastname: Boissonneault
authors.forename: L J
authors.initials: LJ
authors.lastname: Fiscus
authors.forename: M E
authors.initials: ME
authors.lastname: Marra
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000633:toxicity; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007930:Leucine / Q000378:metabolism; D010084:Oxidation-Reduction; D010539:Permeability; D013936:Thymidine / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D005227:Fatty Acids; D014810:Vitamin E; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D007930:Leucine; D013936:Thymidine