title: Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells: involvement of nuclear factor kappa B, Bax and Bcl-2.
abstract: Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance, leading to potential cell damage. Reactive oxygen species such as superoxide radicals, hydroxyl radicals and hydrogen peroxide may act also as secondary intermediaries in intracellular signaling leading to cell death. The neuroprotective effect of melatonin has been observed both in vivo and in vitro. The objective of this research, therefore, was to better understand the cellular mechanisms of neuronal cell degeneration induced via oxidative stress and the protective roles of melatonin on this cell death. In the present study, the effects of melatonin on H(2)O(2)-induced neuronal cell degeneration in human dopaminergic neuroblastoma SH-SY5Y cultured cells were investigated. The results showed that H(2)O(2) significantly decreased cell viability and melatonin reversed the toxic effects of H(2)O(2). An inhibition of caspase enzyme activity by Ac-DEVD-CHO, a caspase-3 inhibitor, significantly increased cell viability in H(2)O(2)-treated cells. The phosphorylation of transcription factors, nuclear factor kappa B (NF-kappaB) was increased in H(2)O(2)-treated cells and this effect was abolished by melatonin. Translocation of phosphorylated NF-kappaB to perinuclear and nuclear sites, estimated using immunofluorescence, occurred to a greater extent in H(2)O(2)-treated cells than in untreated control cells and again this effect was abolished by melatonin. In addition, induction of Bcl-2 and Bax proteins was demonstrated in SH-SY5Y cultured cells treated with H(2)O(2), whereas the induction of Bax but not Bcl-2 was diminished by melatonin. In light of these finding, it is possible that the antioxidative stress effect of melatonin associated with inhibition of Bax expression, may offer a means of treating neuronal degeneration and disease.
authors.affiliation: Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom, Thailand. grbcs@mahidol.ac.th
authors.forename: Banthit
authors.initials: B
authors.lastname: Chetsawang
authors.forename: Chorkaew
authors.initials: C
authors.lastname: Putthaprasart
authors.forename: Pansiri
authors.initials: P
authors.lastname: Phansuwan-Pujito
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D016328:NF-kappa B; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D008550:Melatonin