title: Protective effect of melatonin on methamphetamine-induced apoptosis in glioma cell line.
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.
authors: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors: Pichaya
authors: P
authors: Jumnongprakhon
authors: Piyarat
authors: P
authors: Govitrapong
authors: Chainarong
authors: C
authors: Tocharus
authors: Wanida
authors: W
authors: Tungkum
authors: Jiraporn
authors: J
authors: Tocharus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D053144:Cell Nucleus Shape / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008694:Methamphetamine / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D008694:Methamphetamine; D045304:Cytochromes c; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D008550:Melatonin
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