Membrane lipid modification by polyunsaturated fatty acids sensitizes oligodendroglial OLN-93 cells against oxidative stress and promotes up-regulation of heme oxygenase-1 (HSP32).
Polyunsaturated fatty acids (PUFA) are highly abundant in brain tissue, and docosahexaenoic acid (DHA) might protect cells from oxidative stress (OS) during inflammation and demyelinating disorders, but also might exert pro-oxidant effects. Here we investigated if PUFA supplements lead to heat shock protein induction, altered cell survival properties and stress responses to OS exerted by hydrogen peroxide in oligodendroglial OLN-93 cells. The data show that supplements of various fatty acids (FA) with 18-22 carbons chain length and 2-6 double bonds led to PUFA enrichment in cellular membranes. Depending on the degree of desaturation, FA-supplements caused the up-regulation of heme oxygenase-1 (HSP32), a stress protein inducible by OS, and an increase in sensitivity to hydrogen peroxide-treatment. DHA, with the highest number of double bonds, was most effective. Co-treatment with DHA and the lipophilic vitamin E analogue alpha-tocopherol, suppressed heme oxygenase-1 up-regulation and cell survival was restored. Analysis of the lipid profile demonstrates that alpha-tocopherol not only has antioxidant capacities, but also directly modified the PUFA profile in cell membranes. Enrichment with higher omega-3, -6 and -9 PUFA and an increase in the biosynthesis rate of very long chain fatty acids, mainly changed the FA profile of ethanolamine and serine phosphoglycerides.
Brand
Annette
A
Institute of Brain Chemistry and Human Nutrition School of Medicine, London Metropolitan University, N7 8DB London, UK. annette.brand@gmx.net
Bauer
Nina G
NG
Hallott
Amanda
A
Goldbaum
Olaf
O
Ghebremeskel
Kebreab
K
Reifen
Ram
R
Richter-Landsberg
Christiane
C
D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008563:Membrane Lipids / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D024502:alpha-Tocopherol / Q000494:pharmacology
D000199:Actins; D000975:Antioxidants; D005231:Fatty Acids, Unsaturated; D008563:Membrane Lipids; D017392:Thiobarbituric Acid Reactive Substances; D014404:Tubulin; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D024502:alpha-Tocopherol