Melatonin reduces induction of Bax, caspase and cell death in methamphetamine-treated human neuroblastoma SH-SY5Y cultured cells.
Several studies demonstrated that methamphetamine (MA)-treated human neuroblastoma cells exhibit increased oxidative stress, which regulates intracellular signaling cascades leading to cell death. Melatonin has a potential as a direct free radical scavenger and protects against cell death caused by MA. The objective of this study was to investigate the neuroprotective properties of melatonin on MA-induced induction of death signaling cascade and neuronal cell degeneration in human neuroblastoma SH-SY5Y cultured cells. The results of the present study demonstrate that MA significantly reduced cell viability in SH-SY5Y cultured cells. Desipramine, a monoamine uptake blocker, and melatonin reversed the toxic effect of MA in reducing cell viability. Induction of Bax, Bcl-2 and cleaved caspase-3 protein levels were observed in SH-SY5Y cultured cells treated with MA, whereas the induction of Bax and cleaved caspase-3 was diminished by melatonin. Visualization of the induction of Bax using immunofluorescence but a reduction in mitochondrial sites using red-fluorescent mitochondria-staining dye was more obviously apparent in MA-treated cells than in untreated control cells and, again, this effect was abolished by melatonin. These findings demonstrate important roles of Bax and caspase in death signaling cascade, and the protective effects of melatonin in MA-treated SH-SY5Y cells.
Wisessmith
Wilaiwan
W
Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom, Thailand.
Phansuwan-Pujito
Pansiri
P
Govitrapong
Piyarat
P
Chetsawang
Banthit
B
D053148:Caspase 3 / Q000096:biosynthesis*; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008694:Methamphetamine / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
C494826:BAX protein, human; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D008694:Methamphetamine; D053148:Caspase 3; D008550:Melatonin; D003891:Desipramine