1-Methyl-4-phenyl-pyridinium ion-induced oxidative stress, c-Jun phosphorylation and DNA fragmentation factor-45 cleavage in SK-N-SH cells are averted by selegiline.
Parkinson's disease is a progressive neurodegenerative disorder, associated with the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Recent studies have shown that c-Jun-N terminal kinase pathways might be involved in the oxidative stress-induced neuronal demise. In addition, there are several studies demonstrating that selegiline protects neural cell degeneration. In view of the above, the toxic effects of MPP(+) and the protective roles of selegiline were studied in cultures of human neuroblastoma (SK-N-SH) cell lines in the present study. MPP(+) significantly decreased cell viability but increased reactive oxygen species formation and lipid peroxidation, and the said effects were attenuated by selegiline. MPP(+) did not change the total levels of c-Jun but enhanced phosphorylation of c-Jun at Ser73 and cleavage of DNA fragmentation factor 45, which were diminished by selegiline. MPP(+)-treated SK-N-SH cells exhibited an irregularly shaped nuclear chromatin or DNA fragmentation, which was abolished by selegiline. These data suggest that c-Jun-N terminal kinase pathways are involved in oxidative stress-induced dopaminergic neuronal degeneration and pretreatment with selegiline affords neuroprotection by inhibiting these cell death-signaling pathways.
Chetsawang
Banthit
B
Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakhonpathom 73170, Thailand. grbcs@mahidol.ac.th
Kooncumchoo
Patcharee
P
Govitrapong
Piyarat
P
Ebadi
Manuchair
M
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D006540:Herbicides; D018696:Neuroprotective Agents; D011506:Proteins; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; C109664:caspase-activated DNase inhibitor; D012642:Selegiline; D012694:Serine; D048031:JNK Mitogen-Activated Protein Kinases; D015655:1-Methyl-4-phenylpyridinium