Modulation of glutathione peroxidase activity in human vascular endothelial cells by fatty acids and the cytokine interleukin-1 beta.

ABSTRACT

Objectives of this study were (a) to assess the extent of oxidative stress elicited in human endothelial cells by n-3, n-6 and n-9 mono- and polyunsaturated fatty acids and by interleukin-1 beta and (b) to determine how such stress influenced glutathione peroxidase (GSHPx) activity. Fatty acids were co-incubated with human vascular endothelial cells (HUVEC) for 24 h. Lipid peroxidation, monitored as conjugated diene (CD) formation, increased 3-4-fold with increasing eicosapentaenoic and docosahexaenoic acids 2-3-fold with linoleic acid; decreased by 50% with arachidonic acid and was unchanged with oleic acid. Changes in glutathione peroxidase activity mirrored conjugated diene formation in the HUVEC incubated with fatty acids. Interleukin-1 beta also increased glutathione peroxidase and conjugated diene formation; the latter increased enzyme activity dose-dependently suggesting a possible role for this oxidation product in the induction of glutathione peroxidase activity. The ability of fish oil fatty acids to induce antioxidant enzymes, particularly those of the glutathione redox system, may be an important mechanism protecting cells and tissues against oxidative and inflammatory cytokine elicited damage.