Endogenous eicosanoids modulate cell growth and the expression of immediate early response genes.
Experiments were performed in rat mesangial cells indicating that endogenous non-cyclooxygenase metabolites of AA act to modulate the mitogenic response. Irrespective of the mitogen used, metabolism of AA by LO and/or CP 450 influences induction of cell growth and expression of the immediate early response genes c-fos and Egr-1. In accordance with other reports (3,4) on the influence of eicosanoids on gene expression, our observations indicate that endogenous eicosanoids may act as intracellular mediators. In the mitogenic response, at least two mechanisms of modulation seem possible: i) AA and its metabolites may act by modulating other 2nd messenger systems or ii) eicosanoids may directly regulate the expression of growth-related genes, e.g. by interacting with a fatty acid response element in the promoter region of respective genes.
Sellmayer
A
A
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Universität München, FRG.
Weber
P C
PC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015777:Eicosanoids / Q000502:physiology*; D015870:Gene Expression; D016762:Genes, fos / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D017874:Immediate-Early Proteins; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D015777:Eicosanoids; D017874:Immediate-Early Proteins; D016859:Lipoxygenase Inhibitors; D014157:Transcription Factors; D016718:Arachidonic Acid; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D008084:Lipoxygenase