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

Baek Soo Han, Jai Sung Noh, Byoung Joo Gwag, Young Jun Oh

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)99-102
Number of pages4
JournalNeuroscience Letters
Volume341
Issue number2
DOIs
Publication statusPublished - 2003 May 1

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1-Methyl-4-phenylpyridinium
Oxidopamine
Cell Death
Neurons
Chromatin
Neurotoxins
Mitochondrial Swelling
Caspase Inhibitors
Acetylcysteine
Caspases
Electron Microscopy
Antioxidants

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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title = "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",
abstract = "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.",
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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, Baek Soo; Noh, Jai Sung; Gwag, Byoung Joo; Oh, Young Jun.

In: Neuroscience Letters, Vol. 341, No. 2, 01.05.2003, p. 99-102.

Research output: Contribution to journalArticle

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