Melatonin inhibits MPP+-induced caspase-mediated death pathway and DNA fragmentation factor-45 cleavage in SK-N-SH cultured cells.
Neurodegenerative diseases such as Parkinson's disease are illnesses associated with high morbidity and mortality with few, or no effective, options available for their treatment. In addition, the direct cause of selective dopaminergic cell loss in Parkinson's disease has not been clearly understood. Taken together, several studies have demonstrated that melatonin has a neuroprotective effect both in vivo and in vitro. Accordingly, the effects of melatonin on 1-methyl, 4-phenyl, pyridinium ion (MPP(+))-treated cultured human neuroblastoma SK-N-SH cell lines were investigated in the present study. The results showed that MPP(+) significantly decreased cell viability. By contrast, an induction of phosphorylation of c-Jun, activation of caspase-3 enzyme activity, cleavage of DNA fragmentation factors 45 and DNA fragmentation were observed in MPP(+)-treated cells. These changes were diminished by melatonin. These results demonstrate the cellular mechanisms of neuronal cell degeneration induced via c-Jun-N-terminal kinases and caspase-dependent signaling, and the potential role of melatonin on protection of neuronal cell death induced by this neurotoxin.
Chetsawang
Jirapa
J
Department of Anatomy, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. grbcs@mahidol.ac.th
Govitrapong
Piyarat
P
Chetsawang
Banthit
B
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*
D051017:Apoptosis Regulatory Proteins; C109664:caspase-activated DNase inhibitor; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D008550:Melatonin; D015655:1-Methyl-4-phenylpyridinium