Differential regulation of JNK in caspase-3-mediated apoptosis of MPP+-treated primary cortical neurons

Authors

  • Der-Shan Sun,

    Corresponding author
    1. Institute of Human Genetics, Tzu-Chi University, Hualien 970, Taiwan, ROC
    2. Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien 970, Taiwan, ROC
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  • Hsin-Hou Chang

    1. Institute of Human Genetics, Tzu-Chi University, Hualien 970, Taiwan, ROC
    2. Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien 970, Taiwan, ROC
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Corresponding author. Tel.: +886-3-8565301x7388; fax: +886-3-8561422 dssun@mail.tcu.edu.tw

Abstract

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.

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