FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes
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 man...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-06-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520308130 |
| _version_ | 1818740374503424000 |
|---|---|
| author | Rui Lu Jinichi Ito Noriyuki Iwamoto Tomoko Nishimaki-Mogami Shinji Yokoyama |
| author_facet | Rui Lu Jinichi Ito Noriyuki Iwamoto Tomoko Nishimaki-Mogami Shinji Yokoyama |
| author_sort | Rui Lu |
| collection | DOAJ |
| description | 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 α (LXRα) mRNAs in rat astrocytes. Increase of LXRα 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 LXRα, 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 LXRα being mediated by both LXRα expression and an LXRα ligand biosynthesis. |
| first_indexed | 2024-12-18T01:39:43Z |
| format | Article |
| id | doaj.art-183596ec87534718b9b3da4154e3da87 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:39:43Z |
| publishDate | 2009-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-183596ec87534718b9b3da4154e3da872022-12-21T21:25:21ZengElsevierJournal of Lipid Research0022-22752009-06-0150611561164FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytesRui Lu0Jinichi Ito1Noriyuki Iwamoto2Tomoko Nishimaki-Mogami3Shinji Yokoyama4Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Biochemistry and Metabolism, National Institute of Health Sciences, Tokyo 158-8501, JapanDepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Biochemistry and Metabolism, National Institute of Health Sciences, Tokyo 158-8501, JapanDepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Biochemistry and Metabolism, National Institute of Health Sciences, Tokyo 158-8501, JapanDepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Biochemistry and Metabolism, National Institute of Health Sciences, Tokyo 158-8501, JapanDepartment of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Biochemistry and Metabolism, National Institute of Health Sciences, Tokyo 158-8501, JapanFibroblast 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 α (LXRα) mRNAs in rat astrocytes. Increase of LXRα 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 LXRα, 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 LXRα being mediated by both LXRα expression and an LXRα ligand biosynthesis.http://www.sciencedirect.com/science/article/pii/S0022227520308130high density lipoproteincholesteroldirect repeat 4 |
| spellingShingle | Rui Lu Jinichi Ito Noriyuki Iwamoto Tomoko Nishimaki-Mogami Shinji Yokoyama FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes Journal of Lipid Research high density lipoprotein cholesterol direct repeat 4 |
| title | FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes |
| title_full | FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes |
| title_fullStr | FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes |
| title_full_unstemmed | FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes |
| title_short | FGF-1 induces expression of LXRα and production of 25-hydroxycholesterol to upregulate the apoE gene in rat astrocytes |
| title_sort | fgf 1 induces expression of lxrα and production of 25 hydroxycholesterol to upregulate the apoe gene in rat astrocytes |
| topic | high density lipoprotein cholesterol direct repeat 4 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520308130 |
| work_keys_str_mv | AT ruilu fgf1inducesexpressionoflxraandproductionof25hydroxycholesteroltoupregulatetheapoegeneinratastrocytes AT jinichiito fgf1inducesexpressionoflxraandproductionof25hydroxycholesteroltoupregulatetheapoegeneinratastrocytes AT noriyukiiwamoto fgf1inducesexpressionoflxraandproductionof25hydroxycholesteroltoupregulatetheapoegeneinratastrocytes AT tomokonishimakimogami fgf1inducesexpressionoflxraandproductionof25hydroxycholesteroltoupregulatetheapoegeneinratastrocytes AT shinjiyokoyama fgf1inducesexpressionoflxraandproductionof25hydroxycholesteroltoupregulatetheapoegeneinratastrocytes |