FGF-1-Induced Reactions for Biogenesis of apoE-HDL are Mediated by Src in Rat Astrocytes

Abstract

Fibroblast growth factor-1 (FGF-1) is released from astrocytes in stress and stimulates MEK/ERK and PI3K/Akt pathways in autocrine fashion to increase synthesis of cholesterol and 25-OH-cholesterol, and to induce transport and secretion of apoE, respectively. FGF-1-induced phosphorylation of Src, and phosphorylation of MEK, ERK and Ark was inhibited by Src inhibitors in rat astrocytes. Src inhibitors also suppressed FGF-1-induced increase of biosynthesis and release of cholesterol and increase of apolipoprotein E (apoE) secretion. The results were reproduced in rat astrocytoma cells transfected by rat apoE and in 3T3-L1 cells. Down-regulation of Src expression reduced FGF-1-induced phosphorylation of the signalling protein and subsequent reactions. Increase by FGF-1 of messages of apoE and HMG-CoA reductase was not influenced by Src inhibitors or by its down-regulation. We conclude that FGF-1 activates Src for activation of MEK/ERK and PI3K/Akt pathways, while Src may not be involved in enhancement of transcription of the cholesterol-related genes.