Protection against cell death and sustained tyrosine hydroxylase phosphorylation in hydrogen peroxide- and MPP-treated human neuroblastoma cells with melatonin.
Neuroprotective effects of melatonin against oxidative stress-induced neuronal cell degeneration in human SH-SY5Y neuroblastoma cells were investigated in this report. The results demonstrate that exogenous administration of H(2)O(2) and 1-methyl, 4-phenyl, pyridinium ion (MPP(+)) significantly decreased cell viability in SH-SY5Y cultured cells. Desipramine, a monoamine uptake blocker was able to abolish the toxic effects of MPP(+) but not H(2)O(2) in reduction of cell viability. Conversely, melatonin reversed the toxic effects of H(2)O(2) and MPP(+) on cell viability. In addition, the reduction of phosphorylation of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis, and phosphorylation of cyclic AMP responsive element-binding protein by H(2)O(2) and MPP(+) was also diminished by melatonin. These results demonstrate some effective roles of melatonin on neuroprotection and its action on the modulation of tyrosine hydroxylase phosphorylation.
Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakhonpathom, Thailand. grbcs@mahidol.ac.th
Banthit
B
Chetsawang
Jirapa
J
Chetsawang
Piyarat
P
Govitrapong
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000704:Analysis of Variance; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D006861:Hydrogen Peroxide; D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; D015655:1-Methyl-4-phenylpyridinium; D003891:Desipramine