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Protective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line

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Abstract

Methamphetamine (METH) is a highly addictive drug causing neurodegenerative diseases. METH has been known to be neurotoxic by inducing oxidative stress, free radical, and pro-inflammatory cytokines. Previous studies have shown that METH could induce neuron and glial cell death, especially inducing glial cell-mediated neurotoxicity that plays a critical role in stress-induced central nervous system damage. Therefore, the aim of the present study is to explore the mechanisms of METH-induced cell death in the glial cell. METH-induced glial cells death is mediated via mitochondrial damage pathway. METH activates the upregulation of the Bax, cytochrome c, cleavage caspase 9 and 3 proteins, and downregulation of Bcl-XL protein in cascade. Pretreatment with melatonin, a neurohormone secreted by the pineal gland, effectively reduced glial cell death. Moreover, melatonin increased the Bcl-XL/Bax ratio but reduced the level of cytochrome c, cleavage caspase 9 and 3 proteins. Therefore, these results demonstrated that melatonin could reduce the cytotoxic effect of METH by decreasing the mitochondrial death pathway activation in glial cells. This outcome suggests that melatonin might be beneficial as the neuroprotection in neurodegenerative diseases caused by METH or other pathogens.

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References

  • Ajjimaporn A, Shavali S, Ebadi M, Govitrapong P (2008) Zinc rescues dopaminergic SK-N-SH cell lines from methamphetamine-induced toxicity. Brain Res Bull 77:361–366

    Article  CAS  PubMed  Google Scholar 

  • Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA (2006) Melatonin as antioxidant, geroprotector and anticarcinogen. Biochim Biophys Acta 1757:573–589

    Article  CAS  PubMed  Google Scholar 

  • Brito MA, Lima S, Fernandes A, Falcao AS, Silva RFM, Butterfield DA, Brites D (2008) Bilirubin injury to neurons: contribution of oxidative stress and rescue by glycoursodeoxycholic acid. Neurotoxicology 29:259–269

    Article  CAS  PubMed  Google Scholar 

  • Cadet JL, Jayanthi S, Deng X (2005) Methamphetamine-induced neuronal apoptosis involved the activation of multiple death pathway. Neurotox Res 8:199–206

    Article  CAS  PubMed  Google Scholar 

  • Cardinali DP, Pavet P (1998) Basic aspects of melatonin action. Sleep Med Rev 2:175–190

    Article  CAS  PubMed  Google Scholar 

  • Chen TC, Lai KC, Yang JS, Liao CL, Hsia TC, Chen GW, Lin JJ, Lin HJ, Chiu TH, Tang YJ, Chung JG (2009) Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells. Int J Oncol 34:1681–1690

    CAS  PubMed  Google Scholar 

  • Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ (2001) BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8:705–711

    Article  CAS  PubMed  Google Scholar 

  • Chetsawang J, Suwanjang W, Pirompul N, Govitrapong P, Chetsawang B (2012) Calpastatin reduces methamphetamine-induced induction in c-Jun phosphorylation, Bax and cell death in neuroblastoma SH-SY5Y cells. Neurosci Lett 506:7–11

    Article  CAS  PubMed  Google Scholar 

  • Cruickshank CC, Dyer KR (2009) A review of the clinical pharmacology of methamphetamine. Addiction 104:1085–1099

    Article  PubMed  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fantegrossi WE, Ciullo JR, Wakabayashi KT, De La Garza Ii R, Traynor JR, Woods JH (2008) A comparison of the physiological, behavioral, neurochemical and microglial effects of methamphetamine and 3,4-methylenedioxymethamphetamine in the mouse. Neuroscience 151:533–543

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Feng Z, Zhang JT (2004) Protective effect of melatonin on beta-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism. Free Radic Biol Med 37:1790–1801

    Article  CAS  PubMed  Google Scholar 

  • Fernandes A, Silva RFM, Falcao AS, Brito MA, Brites D (2004) Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS. J Neuroimmunol 153:64–75

    Article  CAS  PubMed  Google Scholar 

  • Genc K, Genc S, Kizildag S, Sonmez U, Yilmaz O, Tugyan K, Ergur B, Sonmez A, Buldan Z (2003) Methamphetamine induces oligodendroglial cell death in vitro. Brain Res 982:125–130

    Article  CAS  PubMed  Google Scholar 

  • Gunasingh MJ, Philip JE, Ashok BS, Kirubagaran R, Jebaraj WCE, Davis GDJ, Vignesh S, Dhandayuthapani S, Jayakumar R (2008) Melatonin prevents amyloid protofibrillar induced oxidative imbalance and biogenic amine catabolism. Life Sci 83:96–102

    Article  CAS  PubMed  Google Scholar 

  • Han SH, Chung SY (2000) Melatonin attenuates trimethyltin-induced hippocampal neurodegeneration. Neurobiol Aging 21(Supplement 1):226

    Article  Google Scholar 

  • Hu J, Akama KT, Krafft GA, Chromy BA, Van Eldik LJ (1998) Amyloid-beta peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release. Brain Res 785:195–206

    Article  CAS  PubMed  Google Scholar 

  • Jayanthi S, Deng X, Noailles PA, Ladenheim B, Cadet JL (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 18:238–251

    Article  CAS  PubMed  Google Scholar 

  • Jeong JC, Jang SW, Kim TH, Kwon CH, Kim YK (2010) Mulberry fruit (Moris fructus) extracts induce human glioma cell death in vitro through ROS-dependent mitochondrial pathway and inhibits glioma tumor growth in vivo. Nutr Cancer 62:402–412

    Article  PubMed  Google Scholar 

  • Jockers R, Maurice P, Boutin JA, Delagrange P (2008) Melatonin receptors, heterodimerization, signal transduction and binding sites: what’s new? Br J Pharmacol 154:1182–1195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson M, Hanson GR, Gibb JW (1988) Effects of dopaminergic and serotonergic receptor blockade on neurochemical changes induced by acute administration of methamphetamine and 3,4-methylenedioxymethamphetamine. Neuropharmacology 27:1089–1096

    Article  PubMed  Google Scholar 

  • Jones DC, Prabhakaran K, Li L, Gunasekar PG, Shou Y, Borowitz JL, Isom GE (2003) Cyanide enhancement of dopamine-induced apoptosis in mesencephalic cells involves mitochondrial dysfunction and oxidative stress. Neurotoxicology 24:333–342

    Article  CAS  PubMed  Google Scholar 

  • Karila L, Weinstein A, Aubin HJ, Benyamina A, Reynaud M, Batki SL (2009) Pharmacological approaches to methamphetamine dependence: a focused review. Br J Clin Pharmacol 69:578–592

    Article  Google Scholar 

  • Kitamura O, Takeichi T, Wang EL, Tokunaga I, Ishigami A, Kubo S (2010) Microglial and astrocytic changes in the striatum of methamphetamine abusers. Leg Med 12:57–62

    Article  CAS  Google Scholar 

  • Klongpanichapak S, Phansuwan-Pujito P, Ebadi M, Govitrapong P (2008) Melatonin inhibits amphetamine-induced increase in alpha-synuclein and decrease in phosphorylated tyrosine hydroxylase in SK-N-SH cells. Neurosci Lett 436:309–313

    Article  CAS  PubMed  Google Scholar 

  • Krasnova IN, Cadet JL (2009) Methamphetamine toxicity and messengers of death. Brain Res Rev 60:379–407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • LaVoie MJ, Card JP, Hastings TG (2004) Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity. Exp Neurol 187:47–57

    Article  CAS  PubMed  Google Scholar 

  • Lin AM, Ho LT (2000) Melatonin suppresses iron-induced neurodegeneration in rat brain. Free Radic Biol Med 28:904–911

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Jamison S, Lin W (2012) Interferon-γ activates nuclear factor-κB in oligodendrocytes through a process mediated by the unfolded protein response. PLoS ONE 7:e36408

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu CH, Yang J, Ren JQ, Liu CM, You Z, Liu PK (2013) MRI reveals differential effects of amphetamine exposure on neuroglia in vivo. FASEB J 27:712–724

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Macchi MM, Bruce JN (2004) Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 25:177–195

    Article  CAS  PubMed  Google Scholar 

  • Morrow BA, Roth RH, Redmond DE, Elsworth JD (2011) Impact of methamphetamine on dopamine neurons in primates is dependent on age: implications for development of Parkinson’s disease. Neuroscience 189:277–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mukda S, Vimolratana O, Govitrapong P (2011) Melatonin attenuates the amphetamine-induced decrease in vesicular monoamine transporter-2 expression in postnatal rat striatum. Neurosci Lett 488:154–157

    Article  CAS  PubMed  Google Scholar 

  • O’Neill LAJ, Kaltschmidt C (1997) NF-κB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20:252–258

    Article  PubMed  Google Scholar 

  • Radogna F, Diederich M, Ghibelli L (2010) Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol 80:1844–1852

    Article  CAS  PubMed  Google Scholar 

  • Smith JA, Das A, Ray SK, Banik NL (2011) Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull 87:10–20

    Article  PubMed  Google Scholar 

  • Su L, Zhao B, Lv X, Wang N, Zhao J, Zhang S, Miao J (2007) Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity. Life Sci 80:999–1006

    Article  CAS  PubMed  Google Scholar 

  • Tamagno E, Parola M, Guglielmotto M, Santoro G, Bardini P, Marra L, Tabaton M, Danni O (2003) Multiple signaling events in amyloid β-induced, oxidative stress-dependent neuronal apoptosis. Free Radic Biol Med 35:45–58

    Article  CAS  PubMed  Google Scholar 

  • Thomas DM, Kuhn DM (2005) MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res 1050:190–198

    Article  CAS  PubMed  Google Scholar 

  • Tocharus J, Chongthammakun S, Govitrapong P (2008) Melatonin inhibits amphetamine-induced nitric oxide synthase mRNA overexpression in microglial cell lines. Neurosci Lett 439:134–137

    Article  CAS  PubMed  Google Scholar 

  • Tocharus J, Khonthun C, Chongthammakun S, Govitrapong P (2010) Melatonin attenuates methamphetamine-induced overexpression of pro-inflammatory cytokines in microglial cell lines. J Pineal Res 48:347–352

    Article  CAS  PubMed  Google Scholar 

  • Trejo-Solis C, Palencia G, Zuniga S, Rodriguez-Ropon A, Osorio-Rico L, Luvia ST, Gracia-Mora I, Marquez-Rosado L, Sanchez A, Moreno-Garcia ME, Cruz A, Bravo-Gomez ME, Ruiz-Ramirez L, Rodriguez-Enriquez S, Sotelo J (2005) Cas IIgly induces apoptosis in glioma C6 cells in vitro and in vivo through caspase-dependent and caspase-independent mechanisms. Neoplasia 7:563–574

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tulloch I, Afanador L, Mexhitaj I, Ghazaryan N, GarzaGongora AG, Angulo JA (2011) A single high dose of methamphetamine induces apoptotic and necrotic striatal cell loss lasting up to 3 months in mice. Neuroscience 193:162–169

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a research grant from the Thailand Research Fund (TRF) through RMU 5480011 and Faculty of Medicine Research Fund, Chiang Mai University, Chiang Mai to JT, Senior Research Scholar Fellowship from the TRF to PG and a Mahidol University research grant to PG. We thank Nikon Corporation, Tokyo, Japan and Hollywood International Ltd, Bangkok, Thailand for technical assistant in fluorescent microscope.

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Authors and Affiliations

  1. Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Pichaya Jumnongprakhon & Chainarong Tocharus

  2. Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand

    Piyarat Govitrapong

  3. Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand

    Piyarat Govitrapong

  4. Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, Thailand

    Piyarat Govitrapong

  5. Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand

    Wanida Tungkum

  6. Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Jiraporn Tocharus

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  1. Pichaya Jumnongprakhon
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  2. Piyarat Govitrapong
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Correspondence to Jiraporn Tocharus.

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Jumnongprakhon, P., Govitrapong, P., Tocharus, C. et al. Protective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line. Neurotox Res 25, 286–294 (2014). https://doi.org/10.1007/s12640-013-9419-y

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  • DOI: https://doi.org/10.1007/s12640-013-9419-y

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