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Specific regulation of rat glial cell line-derived neurotrophic factor gene expression by riluzole in C6 glioma cells.

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Caumont, Anne-Sophie [UCL] Octave, Jean-Noël [UCL] Hermans, Emmanuel [UCL]

Contrasting with its robust expression during embryogenesis, the glial cell line-derived neurotrophic factor (GDNF) is repressed in the adult organism. However, rapid induction of this neuronal growth factor is observed following diverse neuronal insults and it is now widely accepted that the control of its expression could constitute a powerful target in neuropharmacology. We investigated the effects of the neuroprotective drug, riluzole, on the GDNF gene expression in glial cells. Exposure of C6 glioma cells to riluzole (1 microM) significantly increased GDNF protein and mRNA levels. Using luciferase reporter gene constructs encoding fragments of the 5' untranslated region of the rat GDNF gene, we demonstrated that riluzole mediates its effect at the transcription level. Furthermore, luciferase assays revealed the presence of a negative regulatory region within the +343/+587 region of exon 1. This region was shown to contribute to the high sensitivity and specificity of the induction mediated by riluzole in the C6 glioma cell line at pharmacologically relevant concentrations. The effects of riluzole were inhibited by the mitogen-activated protein kinase extracellular signal-related kinase (MEK) inhibitor PD 98059. Together, these results indicated that the induction of GDNF release by riluzole in the C6 glioma cells results from the activation of its corresponding gene promoter through a signalling pathway involving MEK activity. This study suggests that the regulation of GDNF gene transcription in glial cells could contribute to the pharmacological properties of riluzole and possibly other neuroprotective drugs.

  1. Kotzbauer Paul T., Lampe Patricia A., Heuckeroth Robert O., Golden Judith P., Creedon Douglas J., Johnson Jr Eugene M., Milbrandt Jeffrey, Neurturin, a relative of glial-cell-line-derived neurotrophic factor, 10.1038/384467a0
  2. Milbrandt Jeffrey, de Sauvage Frederic J, Fahrner Timothy J, Baloh Robert H, Leitner Melanie L, Tansey Malú G, Lampe Patricia A, Heuckeroth Robert O, Kotzbauer Paul T, Simburger Kelli S, Golden Judith P, Davies Jamie A, Vejsada Richard, Kato Ann C, Hynes Mary, Sherman Daniel, Nishimura Merry, Wang Li-Chong, Vandlen Richard, Moffat Barbara, Klein Robert D, Poulsen Kris, Gray Christa, Garces Alain, Henderson Christopher E, Phillips Heidi S, Johnson Eugene M, Persephin, a Novel Neurotrophic Factor Related to GDNF and Neurturin, 10.1016/s0896-6273(00)80453-5
  3. Baloh Robert H, Tansey Malú G, Lampe Patricia A, Fahrner Timothy J, Enomoto Hideki, Simburger Kelli S, Leitner Melanie L, Araki Toshiyuki, Johnson Eugene M, Milbrandt Jeffrey, Artemin, a Novel Member of the GDNF Ligand Family, Supports Peripheral and Central Neurons and Signals through the GFRα3–RET Receptor Complex, 10.1016/s0896-6273(00)80649-2
  4. Lin L. F., Science, 260, 1130 (1993)
  5. Beck Klaus D., Valverde Janet, Alexi Tajrena, Poulsen Kris, Moffat Barbara, Vandlen Richard A., Rosenthal Arnon, Hefti Franz, Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain, 10.1038/373339a0
  6. Arenas Ernest, Trupp Miles, Åkerud Peter, Ibáñez Carlos F., GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo, 10.1016/0896-6273(95)90024-1
  7. Connor B, Dragunow M, The role of neuronal growth factors in neurodegenerative disorders of the human brain, 10.1016/s0165-0173(98)00004-6
  8. Airaksinen Matti S., Saarma Mart, THE GDNF FAMILY: SIGNALLING, BIOLOGICAL FUNCTIONS AND THERAPEUTIC VALUE, 10.1038/nrn812
  9. Scharr Dale G., Sieber Beth-Anne, Dreyfus Cheryl F., Black Ira B., Regional and Cell-Specific Expression of GDNF in Rat Brain, 10.1006/exnr.1993.1207
  10. Springer J, Expression of GDNF mRNA in Rat and Human Nervous Tissue, 10.1006/exnr.1994.1091
  11. Trupp M., Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons, 10.1083/jcb.130.1.137
  12. Moore Mark W., Klein Robert D., Fariñas Isabel, Sauer Hansjorg, Armanini Mark, Phillips Heidi, Reichardt Louis F., Ryan Anne M., Carver-Moore Karen, Rosenthal Arnon, Renal and neuronal abnormalities in mice lacking GDNF, 10.1038/382076a0
  13. Sánchez Marina P., Silos-Santiago Inmaculada, Frisén Jonas, He Bin, Lira Sergio A., Barbacid Mariano, Renal agenesis and the absence of enteric neurons in mice lacking GDNF, 10.1038/382070a0
  14. Brophy P. D., Development, 128, 4747 (2001)
  15. Strömberg Ingrid, Björklund Lars, Johansson Maria, Tomac Andreas, Collins Frank, Olson Lars, Hoffer Barry, Humpel Christian, Glial Cell Line-Derived Neurotrophic Factor Is Expressed in the Developing but Not Adult Striatum and Stimulates Developing Dopamine Neurons in Vivo, 10.1006/exnr.1993.1214
  16. Appel E., Neuroreport, 8, 3309 (1997)
  17. IANNOTTI C, PINGZHANG Y, SHIELDS C, HAN Y, BURKE D, XU X, A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury, 10.1016/j.expneurol.2004.05.033
  18. Matsushita Natsuki, Fujita Yoko, Tanaka Mikiei, Nagatsu Toshiharu, Kiuchi Kazutoshi, Cloning and structural organization of the gene encoding the mouse glial cell line-derived neurotrophic factor, GDNF, 10.1016/s0378-1119(97)00506-4
  19. Grimm L., Holinski-Feder E., Teodoridis J., Scheffer B., Schindelhauer D., Meitinger T., Ueffing M., Analysis of the human GDNF gene reveals an inducible promoter, three exons, a triplet repeat within the 3'-UTR and alternative splice products, 10.1093/hmg/7.12.1873
  20. Woodbury Dale, Schaar Dale G, Ramakrishnan Lakshmi, Black Ira B, Novel structure of the human GDNF gene, 10.1016/s0006-8993(98)00627-1
  21. Baecker Preston A, Lee Walter H, Verity A.Neil, Eglen Richard M, Johnson Randolph M, Characterization of a promoter for the human glial cell line-derived neurotrophic factor gene, 10.1016/s0169-328x(99)00106-0
  22. Tanaka Mikiei, Ito Sachiko, Kiuchi Kazutoshi, Novel alternative promoters of mouse glial cell line-derived neurotrophic factor gene, 10.1016/s0167-4781(00)00218-9
  23. Hisaoka Kazue, Nishida Akira, Koda Tetsuzo, Miyata Masahiko, Zensho Hidenobu, Morinobu Shigeru, Ohta Mitsuhiro, Yamawaki Shigeto, Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells : Antidepressants induce GDNF synthesis/release, 10.1046/j.1471-4159.2001.00531.x
  24. Tang Yu Ping, Ma Yun Li, Chao Chih Chang, Chen Kai Yi, Lee Eminy H.Y., Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (?)-deprenyl and melatonin treatments, 10.1002/(sici)1097-4547(19980901)53:5<593::aid-jnr9>3.0.co;2-4
  25. Mizuta Ikuko, Ohta Mitsuhiro, Ohta Kiyoe, Nishimura Masataka, Mizuta Eiji, Hayashi Kyozo, Kuno Sadako, Selegiline and Desmethylselegiline Stimulate NGF, BDNF, and GDNF Synthesis in Cultured Mouse Astrocytes, 10.1006/bbrc.2000.4037
  26. Ohta Mitsuhiro, Mizuta Ikuko, Ohta Kiyoe, Nishimura Masataka, Mizuta Eiji, Hayashi Kyozo, Kuno Sadako, Apomorphine Up-Regulates NGF and GDNF Synthesis in Cultured Mouse Astrocytes, 10.1006/bbrc.2000.2732
  27. Mizoule J., Meldrum B., Mazadier Martine, Croucher M., Ollat Catherine, Uzan A., Legrand J.-J., Gueremy C., Le Fur G., 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission—I, 10.1016/0028-3908(85)90011-5
  28. Benavides J, 2-Amino-6-trifluoromethoxy benzothiazole, a possible antagonist of excitatory amino acid neurotransmission—II Biochemical properties, 10.1016/0028-3908(85)90196-0
  29. Doble A., The pharmacology and mechanism of action of riluzole, 10.1212/wnl.47.6_suppl_4.233s
  30. Zona C, Siniscalchi A, Mercuri N.B, G. Bernardi, Riluzole interacts with voltage-activated sodium and potassium currents in cultured rat cortical neurons, 10.1016/s0306-4522(97)00604-0
  31. Wokke John, Riluzole, 10.1016/s0140-6736(96)03181-9
  32. Howard R S, Management of motor neurone disease, 10.1136/pmj.78.926.736
  33. Malgouris C., J. Neurosci., 9, 3720 (1989)
  34. Araki Tsutomu, Kumagai Toshihiko, Tanaka Katsuyuki, Matsubara Mitsunobu, Kato Hiroyuki, Itoyama Yasuto, Imai Yutaka, Neuroprotective effect of riluzole in MPTP-treated mice, 10.1016/s0006-8993(01)02944-4
  35. Suter-Crazzolara Clemens, Unsicker Klaus, GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells, 10.1016/0169-328x(96)00089-7
  36. Verity A. N., J. Neurochem., 70, 531 (1998)
  37. Hisaoka Kazue, Nishida Akira, Takebayashi Minoru, Koda Tetsuzo, Yamawaki Shigeto, Nakata Yoshihiro, Serotonin increases glial cell line-derived neurotrophic factor release in rat C6 glioblastoma cells, 10.1016/j.brainres.2004.01.009
  38. Armstrong Kristen J., Niles Lennard P., Induction of GDNF mRNA expression by melatonin in rat C6 glioma cells : , 10.1097/00001756-200203250-00023
  39. Mosmann Tim, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, 10.1016/0022-1759(83)90303-4
  40. Tanaka Mikiei, Ito Sachiko, Matsushita Natsuki, Mori Nozomu, Kiuchi Kazutoshi, Promoter analysis and characteristics of the 5′-untranslated region of the mouse glial cell line-derived neurotrophic factor gene, 10.1016/s0169-328x(00)00250-3
  41. Tanaka Mikiei, Ito Sachiko, Kiuchi Kazutoshi, The 5′-untranslated region of the mouse glial cell line-derived neurotrophic factor gene regulates expression at both the transcriptional and translational levels, 10.1016/s0169-328x(01)00125-5
  42. Dudley D. T., Proc. Natl Acad. Sci. USA, 92, 7686 (1995)
  43. DAVIES Stephen P., REDDY Helen, CAIVANO Matilde, COHEN Philip, Specificity and mechanism of action of some commonly used protein kinase inhibitors, 10.1042/0264-6021:3510095
  44. Peluffo H, Estevez A, Barbeito L, Stutzmann J.M, Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers, 10.1016/s0304-3940(97)00384-4
  45. Mizuta Ikuko, Ohta Mitsuhiro, Ohta Kiyoe, Nishimura Masataka, Mizuta Eiji, Kuno Sadako, Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes, 10.1016/s0304-3940(01)02098-5
  46. Koh Jae-Young, Kim Dae-Kyong, Hwang Jee Yeon, Kim Yang Hee, Seo Ji Heui, Antioxidative and Proapoptotic Effects of Riluzole on Cultured Cortical Neurons, 10.1046/j.1471-4159.1999.0720716.x
  47. Storch Alexander, Burkhardt Katrin, Ludolph Albert C., Schwarz Johannes, Protective Effects of Riluzole on Dopamine Neurons : Involvement of Oxidative Stress and Cellular Energy Metabolism, 10.1046/j.1471-4159.2000.0752259.x
  48. Yamagata Kazuo, Tagami Motoki, Torii Yasuyoshi, Takenaga Fumio, Tsumagari Shigehisa, Itoh Shingo, Yamori Yukio, Nara Yasuo, Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes, 10.1002/glia.10180
  49. Kokaia Z., Eur. J. Neurosci., 6, 587 (1994)
  50. Leingartner A., Eur. J. Neurosci., 6, 1149 (1994)
  51. Racke Margaret M, Mason Pamela J, Johnson Michael P, Brankamp Robert G, Linnik Matthew D, Demonstration of a second pharmacologically active promoter region in the NGF gene that induces transcription at exon 3, 10.1016/0169-328x(96)00096-4
  52. Kozak M., An analysis of vertebrate mRNA sequences: intimations of translational control, 10.1083/jcb.115.4.887
  53. Jackson Mandy, Lladó Jerònia, Rothstein Jeffrey D, Therapeutic developments in the treatment of amyotrophic lateral sclerosis, 10.1517/13543784.11.10.1343
  54. Koyama Yutaka, Tsujikawa Kimiko, Matsuda Toshio, Baba Akemichi, Endothelin-1 stimulates glial cell line-derived neurotrophic factor expression in cultured rat astrocytes, 10.1016/s0006-291x(03)00491-1
  55. Aronica E., Acta Neuropathol. (Berl.), 105, 515 (2003)
Bibliographic reference Caumont, Anne-Sophie ; Octave, Jean-Noël ; Hermans, Emmanuel. Specific regulation of rat glial cell line-derived neurotrophic factor gene expression by riluzole in C6 glioma cells.. In: Journal of neurochemistry, Vol. 97, no. 1, p. 128-39 (2006)
Permanent URL http://hdl.handle.net/2078.1/10509