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A distinct death mechanism is induced by 1-methyl-4-phenylpyridinium or by 6-hydroxydopamine in cultured rat cortical neurons: degradation and dephosphorylation of tau.

Han, BS; Noh, JS; Gwag, BJ; Oh, YJ
Neuroscience letters, 341(2):99-102, 2003
Journal Title
Neuroscience letters
We examined whether the well-known neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium ion (MPP(+)) recruit distinct cell death mechanisms using primary cultured neurons derived from day 16 embryonic rat cortices. Electron microscopy revealed that cell death induced by both 6-OHDA and MPP(+) was typified by a condensation of chromatin while prominent mitochondrial swelling was observed only in those cells treated with MPP(+). Co-treatment of cells with a pan-caspase inhibitor, Z-VAD-fmk, attenuated 6-OHDA-induced chromatin condensation and neuronal death. Co-treatment with such antioxidants as N-acetylcysteine or Mn-TBAP also suppressed 6-OHDA-induced cell death. None of these treatments attenuated MPP(+)-induced cell death although caspase inhibition abolished MPP(+)-induced chromatin condensation. Interestingly, in these paradigms of cell death, the N-terminus of tau was specifically cleaved and the levels of phosphorylated tau were markedly decreased following 6-OHDA treatment. By contrast, the C-terminus of tau was cleaved in MPP(+)-induced cell death while the levels of phosphorylated tau remained largely unaltered. Taken together, our results indicate that distinct cellular mechanisms appear to underlie neurotoxin-induced cortical neuronal cell death.
MeSH terms
1-Methyl-4-phenylpyridinium/toxicity*Acetylcysteine/pharmacologyAmino Acid Chloromethyl Ketones/pharmacologyAnimalsAnimals, NewbornApoptosis*Cell Culture TechniquesCerebral Cortex/metabolismCerebral Cortex/pathologyCysteine Proteinase Inhibitors/pharmacologyDisease Models, AnimalDrug InteractionsFree Radical Scavengers/pharmacologyMicroscopy, ElectronMitochondria/drug effectsNeurons/drug effects*Neurons/metabolismNeurons/pathologyNeurons/ultrastructureOxidopamine/toxicity*Peptide Fragments/drug effectsPeptide Fragments/metabolismPhosphorylationRatsRats, Sprague-DawleySuperoxide Dismutase/pharmacologyTime Factorstau Proteins/metabolism*
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Psychiatry & Behavioural Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
노, 재성곽, 병주
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