한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제15권2호
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  • Pages.173-178
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  • 2011
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  • 2465-9525(pISSN)
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  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
권호 표지

MDMA (Ecstasy) Induces Egr-1 Expression and Inhibits Neuronal Differentiation

  • 투고 : 2011.04.29
  • 심사 : 2011.06.16
  • 발행 : 2011.06.30
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초록

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a potent monoaminergic neurotoxin with the potential to cause serotonergic neurotoxicity, but has become a popular recreational drug. Little has been known about the cellular effects induced by MDMA. This report shows that MDMA inhibits neuronal cell growth and differentiation. MDMA suppressed neuronal cell growth. The results of quantitative real-time PCR analysis showed that Egr-1 expression is elevated in mouse embryo and neuroblastoma cells after MDMA treatment. Transiently transfected Egr-1 interfered with the neuronal differentiation of neuroblastoma cells such as SH-SY5Y and PC12 cells. These findings provide evidence that the abuse of MDMA during pregnancy may impair neuronal development via an induction of Egr-1 over-expression.

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참고문헌

  1. Baron V, Adamson ED, Calogero A, Ragona G, Mercola D (2005) The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFb1, PTEN, p53 and fibronectin. Cancer Gene Ther 13:115-124.
  2. Broening HW, Morford LL, Inman-Wood SL, Fukumura M, Vorhees CV (2001) 3,4-Methylenedioxymethamphetamine (ecstasy)-induced learning and memory impairments depend on the age of exposure during early development. J Neurosci 21:3228-3235.
  3. Bronson ME, Jiang W, Clark CR, DeRuiter J (1994) Effects of designer drugs on the chicken embryo and 1-dayold chicken. Brain Res Bull 34:143-150. https://doi.org/10.1016/0361-9230(94)90011-6
  4. Campbell NG, Koprich JB, Kanaan NM, Lipton JW (2006) MDMA administration to pregnant Sprague-Dawley rats results in its passage to the fetal compartment. Neurotoxicol Teratol 28:459-465. https://doi.org/10.1016/j.ntt.2006.05.006
  5. Chae M, Rhee GS, Jang IS, Kim K, Lee JH, Lee SY, Kim M, Yang J, Park J, Lee SH (2009) ATG5 expression induced by MDMA(Ecstasy), interferes with neuronal differentiation of neuroblastoma cells. Mol Cells 27: 571-575. https://doi.org/10.1007/s10059-009-0075-2
  6. Cole JC, Sumnall HR (2003) Altered states: the clinical effects of Ecstasy. Pharmacol Ther 98:35-58. https://doi.org/10.1016/S0163-7258(03)00003-2
  7. Demir O, Kurnaz IA (2008) Wildtype Elk-1, but not a SUMOylation mutant, represses egr-1 expression in SHSY5Y neuroblastomas. Neurosci Lett 437:20-24. https://doi.org/10.1016/j.neulet.2008.03.064
  8. Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V, Gallego C, Comella JX. (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75:991-1003.
  9. Fahmy RG, Dass CR, Sun LQ, Chesterman CN, Khachigian LM (2003) Transcription factor Egr-1 supports FGFdependent angiogenesis during neovascularization and tumor growth. Nat Med 9:1026-1032. https://doi.org/10.1038/nm905
  10. Galineau L, Belzung C, Kodas E, Bodard S, Guilloteau D, Chalon S (2005) Prenatal 3,4-methylenedioxymethamphetamine (ecstasy) exposure induces long-term alterations in the dopaminergic and serotonergic functions in the rat. Brain Res Dev Brain Res 154:165-176. https://doi.org/10.1016/j.devbrainres.2004.10.012
  11. Huang RP, Fan Y, de Belle I, Niemeyer C, Gottardis MM, Mercola D, Adamson ED (1997) Decreased Egr-1 expression in human, mouse and rat mammary cells and tissues correlates with tumor formation. Int J Cancer 72:102-109. https://doi.org/10.1002/(SICI)1097-0215(19970703)72:1<102::AID-IJC15>3.0.CO;2-L
  12. Kim HS, Yumkham S, Kim SH, Yea K, Shin YC, Ryu SH, Suh PG (2006) Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway. Exp Mol Med 38:85-93. https://doi.org/10.1038/emm.2006.10
  13. Kim S, Ghil SH, Kim SS, Myeong HH, Lee YD, Suh-Kim H (2002) Overexpression of neurogenin1 induces neurite outgrowth in F11 neuroblastoma cells. Exp Mol Med 34:469-475. https://doi.org/10.1038/emm.2002.65
  14. McElhatton PR, Bateman DN, Evans C, Pughe KR, Thomas SH (1999) Congenital anomalies after prenatal ecstasy exposure. Lancet 354:1441-1442. https://doi.org/10.1016/S0140-6736(99)02423-X
  15. Miguel P, Rosario L, Arturo P, Angel S, Ana P (2003) The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells. Biochem J 373:739-746. https://doi.org/10.1042/BJ20021918
  16. Pignatelli M, Luna-Medina R, Perez-Rendon A, Santos A, Perez-Castillo A (2003) The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells. Biochem J 373:739-746. https://doi.org/10.1042/BJ20021918
  17. Ragione FD, Cucciolla V, Criniti V, Indaco S, Borriello A, Zappia V (2003) p21Cip1 gene expression is modulated by Egr1; a novel regulatory mechanism involved in the resveratrol antiproliferative effect. J Biol Chem 278:23360-23368. https://doi.org/10.1074/jbc.M300771200
  18. Silverman ES, Collins T (1999) Pathways of Egr-1-mediated gene transcription in vascular biology. Am J Pathol 154:665-670. https://doi.org/10.1016/S0002-9440(10)65312-6
  19. Sumnall HR, Jerome L, Doblin R, Mithoefer MC (2004) Response to: Parrott AC, Buchanan T, Heffernan TM, Scholey A, Ling J, Rodgers J (2003) Parkinson's disorder, psychomotor problems and dopaminergic neurotoxicity in recreational ecstasy/MDMA users. Psychopharmacology 171:229-230. https://doi.org/10.1007/s00213-003-1599-3
  20. Thiel G, Cibelli G (2002) Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol 193:287-292. https://doi.org/10.1002/jcp.10178
  21. Wilson MA, Ricaurte GA, Molliver ME (1989) Distinct morphologic classes of serotonergic axons in primates exhibit differential vulnerability to the psychotropic drug 3,4-methylenedioxymethamphetamine. Neuroscience 28: 121-137. https://doi.org/10.1016/0306-4522(89)90237-6