title: Melatonin prevents cytosolic calcium overload, mitochondrial damage and cell death due to toxically high doses of dexamethasone-induced oxidative stress in human neuroblastoma SH-SY5Y cells.
abstract: Stressor exposure activates the hypothalamic-pituitary-adrenal (HPA) axis and causes elevations in the levels of glucocorticoids (GC) from the adrenal glands. Increasing evidence has demonstrated that prolonged exposure to high GC levels can lead to oxidative stress, calcium deregulation, mitochondrial dysfunction and apoptosis in a number of cell types. However, melatonin, via its antioxidant activity, exhibits a neuroprotective effect against oxidative stress-induced cell death. Therefore, in the present study, we explored the protective effect of melatonin in GC-induced toxicity in human neuroblastoma SH-SY5Y cells. Cellular treatment with the toxically high doses of the synthetic GC receptor agonist, dexamethasone (DEX) elicited marked decreases in the levels of glutathione and increases in ROS production, lipid peroxidation and cell death. DEX toxicity also induced increases in the levels of cytosolic calcium and mitochondrial fusion proteins (Mfn1 and Opa1) but decreases in the levels of mitochondrial fission proteins (Fis1 and Drp1). Mitochondrial damage was observed in large proportions of the DEX-treated cells. Pretreatment of the cells with melatonin substantially prevented the DEX-induced toxicity. These results suggest that melatonin might exert protective effects against oxidative stress, cytosolic calcium overload and mitochondrial damage in DEX-induced neurotoxicity.
authors.affiliation: Center for Innovation Development and Technology Transfer, Faculty of Medical Technology Mahidol University, Nakhonpathom, 73170, Thailand; Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom, 73170, Thailand.
authors.forename: Wilasinee
authors.initials: W
authors.lastname: Suwanjang
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, UCL, Queen Square, London, WC1N 3BG, UK.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
authors.affiliation: Department of Pathology, Faculty of Medicine Siriraj Hospital, Bangkok, 10700, Thailand.
authors.forename: Komgrid
authors.initials: K
authors.lastname: Charngkaew
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom, 73170, Thailand; Center for Neuroscience and Department for Pharmacology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom, 73170, Thailand. Electronic address: banthit.che@mahidol.ac.th.
authors.forename: Banthit
authors.initials: B
authors.lastname: Chetsawang
mesh_terms: D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003907:Dexamethasone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009447:Neuroblastoma / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003907:Dexamethasone; D008550:Melatonin; D002118:Calcium
keywords: Calcium; Dexamethasone; Melatonin; Mitochondria; Neurotoxicity; Stress