Differential regulation of JNK in caspase-3-mediated apoptosis of MPP(+)-treated primary cortical neurons.
MPTP (1-methyl-1,2,3,6-tetrahydropyridine), a chemical contaminant of synthetic heroin, induces neuropathological changes with clinical features similar to idiopathic Parkinson's disease. The mechanism by which MPTP and its metabolite MPP(+)(1-methyl-4-phenylpyridinium) induces neuronal cell death remains unclear. We employed primary cortical/telencephalon neuronal cultures to investigate the potential role of caspase and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) pathways in MPP(+)-induced neuronal death. DNA fragmentation and caspase-3 activity analysis showed that cortical neuronal cells underwent apoptosis after MPP(+)treatment. However, a basal level of apoptotic cells was also observed in untreated cultures. Interestingly, JNK activity increased in untreated cultures over time, whereas it was down-regulated after MPP(+)treatment. This indicates that the JNK pathways could be differentially regulated in different apoptotic processes.
Sun
Der-Shan
DS
Institute of Human Genetics, Tzu-Chi University, 970 Hualien, Taiwan, ROC. dssun@mail.tcu.edu.tw
Chang
Hsin-Hou
HH
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D053938:DNA Fragmentation; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D015655:1-Methyl-4-phenylpyridinium