FGF-1-induced reactions for biogenesis of apoE-HDL are mediated by src in rat astrocytes.
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.
Nishida
Tomo
T
Biochemistry, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Ito
Jin-Ichi
J
Nagayasu
Yuko
Y
Yokoyama
Shinji
S
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008954:Models, Biological; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D016220:Fibroblast Growth Factor 1; D019061:src-Family Kinases