title: Melatonin Protects SH-SY5Y Neuronal Cells Against Methamphetamine-Induced Endoplasmic Reticulum Stress and Apoptotic Cell Death.
abstract: Methamphetamine (METH), a psychostimulant with highly neurotoxic effects, has been known to induce neuronal apoptosis in part through an endoplasmic reticulum (ER) stress pathway. Melatonin is an endogenous antioxidant compound that exerts protective effects against several neurodegenerative conditions, including METH-induced neurotoxicity, via various mechanisms. However, the role of melatonin in ER stress is still relatively unclear. In the present study, we investigated ER stress and neuronal apoptosis following METH treatment and the role of melatonin in METH-mediated ER stress-induced cell death in the SH-SY5Y neuroblastoma cell line. We found that METH caused the overexpression of ER stress-related genes, including C/EBP homologous protein and spliced X-box binding protein 1, in dose- and time-dependent manners. Moreover, METH time-dependently activated caspase-12 and -3, leading to cellular apoptosis. Furthermore, we demonstrated that pretreatment with melatonin attenuated the overexpression of ER stress-related genes and the cleavages of caspase-12 and -3 caused by METH exposure. Flow cytometry revealed that METH-mediated neuronal apoptosis was also prevented by melatonin. These findings suggest the protective effects of melatonin against ER stress and apoptosis caused by METH and other harmful agents.
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom, 73170, Thailand. piyarat.gov@mahidol.ac.th.
authors.forename: Pawaris
authors.initials: P
authors.lastname: Wongprayoon
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom, 73170, Thailand.|Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand.
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000975:Antioxidants; D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D008694:Methamphetamine; C506444:CASP12 protein, human; C505407:CASP3 protein, human; D053454:Caspase 12; D053148:Caspase 3; D008550:Melatonin
keywords: Apoptosis; Endoplasmic reticulum stress; Melatonin; Methamphetamine