title: Melatonin attenuates dexamethasone toxicity-induced oxidative stress, calpain and caspase activation in human neuroblastoma SH-SY5Y cells.
abstract: Glucocorticoids (GCs) have a significant role in the adaptive response of the brain to stress. Increasing evidence has demonstrated that an increase of GC levels may induce neuronal cell death via apoptotic pathways. There is a correlation between over-production of reactive oxygen species (ROS) and an elevation in cytosolic calcium that causes a subsequent increase in the calcium-dependent death-process activation in GC-induced toxicity. Consequently, melatonin, via its antioxidant activity, exhibits a neuroprotective effect against apoptosis induced by intracellular calcium overload. Therefore, in the present study, we explored the protective effect of melatonin in GC-induced toxicity in dopaminergic SH-SY5Y cells. Cellular treatment with the synthetic GCs, dexamethasone (DEX), resulted in a marked decrease in cell viability and in the level of the calpain-inhibitor protein, calpastatin. DEX-induced toxicity also caused an increase in ROS production and the activation of the calcium-dependent cysteine protease, calpain, along with an increase in caspase-3 activation. Pretreatment of the cells with melatonin substantially prevented the decrease in cell viability, over-production of ROS and the activation of calpain and caspase-3, and reversed the depletion in calpastatin levels. These results suggest that melatonin may exert its protective effects against the calpain- and caspase-dependent death process in DEX-induced neurotoxicity.
authors.affiliation: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom, Thailand.
authors.forename: Wilasinee
authors.initials: W
authors.lastname: Suwanjang
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.forename: Banthit
authors.initials: B
authors.lastname: Chetsawang
mesh_terms: D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003907:Dexamethasone; D002154:Calpain; D020169:Caspases; D008550:Melatonin
keywords: Calpain; Cell death; Dexamethasone; Melatonin; Neurons; Oxidative stress