Reference - Detail
| RRC ID | 6610 |
|---|---|
| Author | Lu R, Ito J, Iwamoto N, Nishimaki-Mogami T, Yokoyama S. |
| Title | FGF-1 induces expression of LXRalpha and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes. |
| Journal | J Lipid Res |
| Abstract |
Fibroblast growth factor 1 (FGF-1) enhances apolipoprotein E (apoE) expression and apoE-HDL biogenesis in autocrine fashion in astrocytes (Ito, J., Y. Nagayasu, R. Lu, A. Kheirollah, M. Hayashi, and S. Yokoyama. Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action. J. Lipid Res. 2005. 46: 679-686) associated with healing of brain injury (Tada,T., J-i. Ito, M. Asai, and S. Yokoyama. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse brain. Neurochem. Int. 2004. 45: 23-30). FGF-1 stimulates mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) to increase cholesterol biosynthesis and phosphatidylinositol 3-OH kinase (PI3K)/Akt to enhance apoE-HDL secretion (Ito, J., Y. Nagayasu, K. Okumura-Noji, R. Lu, T. Nishida, Y. Miura, K. Asai, A. Kheirollah, S. Nakaya, and S. Yokoyama. Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes. J. Lipid Res. 2007. 48: 2020-2027). We investigated the mechanism for FGF-1 to upregulate apoE transcription. FGF-1 increased apoE and liver X receptor alpha (LXRalpha) mRNAs in rat astrocytes. Increase of LXRalpha mRNA was suppressed by inhibition of the FGF-1 receptor-1 and MEK/ERK but not by inhibition of PI3K/Akt. The increases of apoE mRNA and apoE-HDL secretion were both inhibited by downregulation or inhibition of LXRalpha, while they were partially suppressed by inhibiting cholesterol biosynthesis. We identified the liver X receptor element responsible for activation of the rat apoE promoter by FGF-1 located between -450 and -320 bp, and the direct repeat 4 (DR4) element in this region (-448 to -433 bp) was responsible for the activation. Chromatin immunoprecipitation analysis supported that FGF-1 enhanced association of LXR with the rat apoE promoter. FGF-1 partially activated the apoE promoter even in the presence of an MEK inhibitor that inhibits the FGF-1-mediated enhancement of cholesterol biosynthesis. On the other hand, FGF-1 induced production of 25-hydroxycholesterol by MEK/ERK as an sterol regulatory element-dependent reaction besides cholesterol biosynthesis. We concluded that FGF-1-induced apoE expression in astrocytes depends on LXRalpha being mediated by both LXRalpha expression and an LXRalpha ligand biosynthesis. |
| Volume | 50(6) |
| Pages | 1156-64 |
| Published | 2009-6-1 |
| DOI | 10.1194/jlr.M800594-JLR200 |
| PII | S0022-2275(20)30813-0 |
| PMID | 19229075 |
| PMC | PMC2681397 |
| MeSH | Animals Apolipoproteins E / genetics* Astrocytes / drug effects* Astrocytes / metabolism* Base Sequence Butadienes / pharmacology Cells, Cultured DNA Primers / genetics DNA-Binding Proteins / genetics* Fibroblast Growth Factor 1 / pharmacology* Gene Expression / drug effects Hydroxycholesterols / metabolism* Liver X Receptors MAP Kinase Signaling System / drug effects Models, Biological Nitriles / pharmacology Orphan Nuclear Receptors Promoter Regions, Genetic RNA, Messenger / genetics RNA, Messenger / metabolism Rats Receptors, Cytoplasmic and Nuclear / genetics* Recombinant Proteins / pharmacology Up-Regulation / drug effects |
| IF | 4.483 |
| Times Cited | 12 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Resource | |
| Human and Animal Cells | BALB/3T3 |