Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription

Masashi Murakami, Hiromi Ito, Kazumi Hagiwara, Misa Kobayashi, Asuka Hoshikawa, Akira Takagi, Tetsuhito Kojima, Keiko Tamiya-Koizumi, Sayaka Sobue, Masatoshi Ichihara, Motoshi Suzuki, Yoshiko Banno, Yoshinori Nozawa, Takashi Murate

Research output: Contribution to journalArticle

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Abstract

Glial cell line-derived neurotrophic factor (GDNF) is important for the development and maintenance of dopamine neurons (Lin et al. [1993] Science 260: 1130-1132). GDNF is neuroprotective in animal models of Parkinson disease, where dopamine neurons show selective degeneration. We previously reported GDNF-induced SPHK1 gene expression in a neuroblastoma cell line, TGW (Murakami et al. [2007] J Neurochem 102: 1585-1594). In the present study, we focused on the regulatory mechanism of GAP43 (GDNF-induced neuronal phenotype) transcription to further elucidate physiological roles of GDNF-induced SPHK1 expression and activity. Stable wild-type (SPHK1-WT) but not dominant-negative SPHK1 (SPHK1-DN) overexpression increased both control- and GDNF-induced GAP43 expression. SPHK1-WT cells showed enhanced GDNF-induced sphingosine 1-phosphate (S1P) secretion compared with mock- and SPHK1-DN cells. Exogenous S1P also increased GAP43 expression. In TGW cells, PD98059, a MEK inhibitor, but not SB203580 (a p38 MAPK inhibitor) and LY294002 (a PI3K inhibitor) inhibited GDNF-induced GAP43 expression, suggesting the MEK/ERK pathway has a major role in GDNF-induced GAP43 transcription. A G-protein-coupled receptor inhibitor, pertussis toxin, and S1P 1 and S1P 3 receptor antagonists (VPC23019 and CAY10444) also inhibited ERK activation. Moreover, both S1P1 and S1P3 were serine-phosphorylated by GDNF, suggesting their activated states. C/EBPβ transcription factor was induced by GDNF, and DNA pull-down and chromatin immunoprecipitation assays revealed the C/EBP binding site between -131 bp and -98 bp from the first exon of GAP43. Taken together, our results showed that in TGW cells, GDNF increased SPHK1 transcription, leading to the production and secretion of S1P. Through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of C/EBPβ to the 5′-promoter.

Original languageEnglish
Pages (from-to)3449-3458
Number of pages10
JournalJournal of Cellular Biochemistry
Volume112
Issue number11
DOIs
Publication statusPublished - 01-11-2011
Externally publishedYes

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Glial Cell Line-Derived Neurotrophic Factor
Transcription
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Signaling System
Dopaminergic Neurons
Neurons
sphingosine kinase
sphingosine 1-phosphate
Dopamine
Lysosphingolipid Receptors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Chromatin Immunoprecipitation
Pertussis Toxin
p38 Mitogen-Activated Protein Kinases
G-Protein-Coupled Receptors
Neuroblastoma
Phosphatidylinositol 3-Kinases
Gene expression
Serine
Chromatin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Murakami, M., Ito, H., Hagiwara, K., Kobayashi, M., Hoshikawa, A., Takagi, A., ... Murate, T. (2011). Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. Journal of Cellular Biochemistry, 112(11), 3449-3458. https://doi.org/10.1002/jcb.23275
Murakami, Masashi ; Ito, Hiromi ; Hagiwara, Kazumi ; Kobayashi, Misa ; Hoshikawa, Asuka ; Takagi, Akira ; Kojima, Tetsuhito ; Tamiya-Koizumi, Keiko ; Sobue, Sayaka ; Ichihara, Masatoshi ; Suzuki, Motoshi ; Banno, Yoshiko ; Nozawa, Yoshinori ; Murate, Takashi. / Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. In: Journal of Cellular Biochemistry. 2011 ; Vol. 112, No. 11. pp. 3449-3458.
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abstract = "Glial cell line-derived neurotrophic factor (GDNF) is important for the development and maintenance of dopamine neurons (Lin et al. [1993] Science 260: 1130-1132). GDNF is neuroprotective in animal models of Parkinson disease, where dopamine neurons show selective degeneration. We previously reported GDNF-induced SPHK1 gene expression in a neuroblastoma cell line, TGW (Murakami et al. [2007] J Neurochem 102: 1585-1594). In the present study, we focused on the regulatory mechanism of GAP43 (GDNF-induced neuronal phenotype) transcription to further elucidate physiological roles of GDNF-induced SPHK1 expression and activity. Stable wild-type (SPHK1-WT) but not dominant-negative SPHK1 (SPHK1-DN) overexpression increased both control- and GDNF-induced GAP43 expression. SPHK1-WT cells showed enhanced GDNF-induced sphingosine 1-phosphate (S1P) secretion compared with mock- and SPHK1-DN cells. Exogenous S1P also increased GAP43 expression. In TGW cells, PD98059, a MEK inhibitor, but not SB203580 (a p38 MAPK inhibitor) and LY294002 (a PI3K inhibitor) inhibited GDNF-induced GAP43 expression, suggesting the MEK/ERK pathway has a major role in GDNF-induced GAP43 transcription. A G-protein-coupled receptor inhibitor, pertussis toxin, and S1P 1 and S1P 3 receptor antagonists (VPC23019 and CAY10444) also inhibited ERK activation. Moreover, both S1P1 and S1P3 were serine-phosphorylated by GDNF, suggesting their activated states. C/EBPβ transcription factor was induced by GDNF, and DNA pull-down and chromatin immunoprecipitation assays revealed the C/EBP binding site between -131 bp and -98 bp from the first exon of GAP43. Taken together, our results showed that in TGW cells, GDNF increased SPHK1 transcription, leading to the production and secretion of S1P. Through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of C/EBPβ to the 5′-promoter.",
author = "Masashi Murakami and Hiromi Ito and Kazumi Hagiwara and Misa Kobayashi and Asuka Hoshikawa and Akira Takagi and Tetsuhito Kojima and Keiko Tamiya-Koizumi and Sayaka Sobue and Masatoshi Ichihara and Motoshi Suzuki and Yoshiko Banno and Yoshinori Nozawa and Takashi Murate",
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Murakami, M, Ito, H, Hagiwara, K, Kobayashi, M, Hoshikawa, A, Takagi, A, Kojima, T, Tamiya-Koizumi, K, Sobue, S, Ichihara, M, Suzuki, M, Banno, Y, Nozawa, Y & Murate, T 2011, 'Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription', Journal of Cellular Biochemistry, vol. 112, no. 11, pp. 3449-3458. https://doi.org/10.1002/jcb.23275

Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. / Murakami, Masashi; Ito, Hiromi; Hagiwara, Kazumi; Kobayashi, Misa; Hoshikawa, Asuka; Takagi, Akira; Kojima, Tetsuhito; Tamiya-Koizumi, Keiko; Sobue, Sayaka; Ichihara, Masatoshi; Suzuki, Motoshi; Banno, Yoshiko; Nozawa, Yoshinori; Murate, Takashi.

In: Journal of Cellular Biochemistry, Vol. 112, No. 11, 01.11.2011, p. 3449-3458.

Research output: Contribution to journalArticle

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T1 - Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription

AU - Murakami, Masashi

AU - Ito, Hiromi

AU - Hagiwara, Kazumi

AU - Kobayashi, Misa

AU - Hoshikawa, Asuka

AU - Takagi, Akira

AU - Kojima, Tetsuhito

AU - Tamiya-Koizumi, Keiko

AU - Sobue, Sayaka

AU - Ichihara, Masatoshi

AU - Suzuki, Motoshi

AU - Banno, Yoshiko

AU - Nozawa, Yoshinori

AU - Murate, Takashi

PY - 2011/11/1

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N2 - Glial cell line-derived neurotrophic factor (GDNF) is important for the development and maintenance of dopamine neurons (Lin et al. [1993] Science 260: 1130-1132). GDNF is neuroprotective in animal models of Parkinson disease, where dopamine neurons show selective degeneration. We previously reported GDNF-induced SPHK1 gene expression in a neuroblastoma cell line, TGW (Murakami et al. [2007] J Neurochem 102: 1585-1594). In the present study, we focused on the regulatory mechanism of GAP43 (GDNF-induced neuronal phenotype) transcription to further elucidate physiological roles of GDNF-induced SPHK1 expression and activity. Stable wild-type (SPHK1-WT) but not dominant-negative SPHK1 (SPHK1-DN) overexpression increased both control- and GDNF-induced GAP43 expression. SPHK1-WT cells showed enhanced GDNF-induced sphingosine 1-phosphate (S1P) secretion compared with mock- and SPHK1-DN cells. Exogenous S1P also increased GAP43 expression. In TGW cells, PD98059, a MEK inhibitor, but not SB203580 (a p38 MAPK inhibitor) and LY294002 (a PI3K inhibitor) inhibited GDNF-induced GAP43 expression, suggesting the MEK/ERK pathway has a major role in GDNF-induced GAP43 transcription. A G-protein-coupled receptor inhibitor, pertussis toxin, and S1P 1 and S1P 3 receptor antagonists (VPC23019 and CAY10444) also inhibited ERK activation. Moreover, both S1P1 and S1P3 were serine-phosphorylated by GDNF, suggesting their activated states. C/EBPβ transcription factor was induced by GDNF, and DNA pull-down and chromatin immunoprecipitation assays revealed the C/EBP binding site between -131 bp and -98 bp from the first exon of GAP43. Taken together, our results showed that in TGW cells, GDNF increased SPHK1 transcription, leading to the production and secretion of S1P. Through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of C/EBPβ to the 5′-promoter.

AB - Glial cell line-derived neurotrophic factor (GDNF) is important for the development and maintenance of dopamine neurons (Lin et al. [1993] Science 260: 1130-1132). GDNF is neuroprotective in animal models of Parkinson disease, where dopamine neurons show selective degeneration. We previously reported GDNF-induced SPHK1 gene expression in a neuroblastoma cell line, TGW (Murakami et al. [2007] J Neurochem 102: 1585-1594). In the present study, we focused on the regulatory mechanism of GAP43 (GDNF-induced neuronal phenotype) transcription to further elucidate physiological roles of GDNF-induced SPHK1 expression and activity. Stable wild-type (SPHK1-WT) but not dominant-negative SPHK1 (SPHK1-DN) overexpression increased both control- and GDNF-induced GAP43 expression. SPHK1-WT cells showed enhanced GDNF-induced sphingosine 1-phosphate (S1P) secretion compared with mock- and SPHK1-DN cells. Exogenous S1P also increased GAP43 expression. In TGW cells, PD98059, a MEK inhibitor, but not SB203580 (a p38 MAPK inhibitor) and LY294002 (a PI3K inhibitor) inhibited GDNF-induced GAP43 expression, suggesting the MEK/ERK pathway has a major role in GDNF-induced GAP43 transcription. A G-protein-coupled receptor inhibitor, pertussis toxin, and S1P 1 and S1P 3 receptor antagonists (VPC23019 and CAY10444) also inhibited ERK activation. Moreover, both S1P1 and S1P3 were serine-phosphorylated by GDNF, suggesting their activated states. C/EBPβ transcription factor was induced by GDNF, and DNA pull-down and chromatin immunoprecipitation assays revealed the C/EBP binding site between -131 bp and -98 bp from the first exon of GAP43. Taken together, our results showed that in TGW cells, GDNF increased SPHK1 transcription, leading to the production and secretion of S1P. Through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of C/EBPβ to the 5′-promoter.

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Murakami M, Ito H, Hagiwara K, Kobayashi M, Hoshikawa A, Takagi A et al. Sphingosine kinase 1/S1P pathway involvement in the GDNF-induced GAP43 transcription. Journal of Cellular Biochemistry. 2011 Nov 1;112(11):3449-3458. https://doi.org/10.1002/jcb.23275