Sellmayer A, Danesch U, Weber P C
Institut für Prophylaxe und Epidemiologie, Kreislaufkrankheiten, Universität München, Germany.
Lipids. 1996 Mar;31 Suppl:S37-40. doi: 10.1007/BF02637048.
Effects of polyunsaturated fatty acids on expression of early-response genes c-fos and Egr-1 and induction of cell growth were assessed in Swiss 3T3 fibroblasts. Stimulation with arachidonic acid increased mRNA levels of c-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 increase c-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 genes c-fos and Egr-1 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.
在瑞士3T3成纤维细胞中评估了多不饱和脂肪酸对早期反应基因c-fos和Egr-1表达以及细胞生长诱导的影响。用花生四烯酸刺激可增加c-fos和Egr-1的mRNA水平。这种效应被与环氧化酶抑制剂预孵育所抑制，并通过添加前列腺素E2（PGE2）得以恢复，PGE2是瑞士3T3成纤维细胞中产生的主要类二十烷酸。PGE2的进一步信号传导由蛋白激酶C依赖性途径介导，因为蛋白激酶C的下调或抑制会降低mRNA水平的增加。与对mRNA水平的刺激作用平行，AA和PGE2也增加了细胞生长，这通过[3H]-胸腺嘧啶核苷的摄取来确定。与花生四烯酸相反，n-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）不会增加c-fos和Egr-1的mRNA水平或细胞生长。此外，初步数据表明，EPA和DHA甚至会降低AA的刺激作用，这与PGE2生成减少有关。总之，我们的数据表明，AA通过转化为PGE2并随后激活蛋白激酶C来增加瑞士3T3成纤维细胞中与生长相关的早期基因c-fos和Egr-1的表达，而n-3脂肪酸不会激活这种信号级联反应。
