Effect of vitamin E on oxysterol- and fatty acid hydroperoxide-induced changes of repair and permeability properties of cultured endothelial cell monolayers.
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)
Hennig
B
B
Department of Nutrition and Food Science, University of Kentucky, Lexington.
Boissonneault
G A
GA
Fiscus
L J
LJ
Marra
M E
ME
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*
D000924:Anticholesteremic Agents; D005227:Fatty Acids; D014810:Vitamin E; C002843:cholesterol hydroperoxide; D002784:Cholesterol; D007930:Leucine; D013936:Thymidine