Effects of different polunsaturated fatty acids on growth-related early gene expression and cell growth |
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Authors: | A Sellmayer U Danesch P C Weber |
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Affiliation: | 1. Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Universit?t München, Pettenkoferstr. 9, 80336, München, Germany 2. Medizinische Klinik Innenstadt, Universit?t München, München, Germany
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Abstract: | Effects of polyunsaturated fatty acids on expression of early-response genesc-fos and Egr-1 and induction of cell growth were assessed in Swiss 3T3 fibroblasts. Stimulation with arachidonic acid increased
mRNA levels ofc-fos and Egr-1. This effect was inhibited by preincubation with cyclooxygenase inhibitors and restored by addition of prostaglandin
E2 (PGE2), the predominant eicosanoid produced in Swiss 3T3 fibroblasts. Further signaling of PGE2 was mediated by a protein kinase C-dependent pathway, since downregulation, or inhibition, of protein kinase C reduced increases
in mRNA levels. Parallel to the stimulatory effects on mRNA levels, AA and PGE2 also increased cell growth, as determined by uptake of 3H]-thymidine. In contrast to arachidonic acid, n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
did not increasec-fos and Egr-1 mRNA levels or cell growth. Furthermore, preliminary data indicate that EPA and DHA even reduce the stimulatory
effect of AA, which is associated with reduced formation of PGE2. In conclusion, our data indicate that AA increases expression of growth-related early genesc-fos and Egr-1 in Swiss 3T3 fibroblasts by its conversion to PGE2 and subsequent activation of protein kinase C, whereas n-3 fatty acids do not activate this signaling cascade. |
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