Mitochondrial Complex I Inhibitor Rotenone Inhibits and Redistributes Vesicular Monoamine Transporter 2 via Nitration in Human Dopaminergic SH-SY5Y Cells

@article{Watabe2008MitochondrialCI,
  title={Mitochondrial Complex I Inhibitor Rotenone Inhibits and Redistributes Vesicular Monoamine Transporter 2 via Nitration in Human Dopaminergic SH-SY5Y Cells},
  author={Masahiko Watabe and Toshio Nakaki},
  journal={Molecular Pharmacology},
  year={2008},
  volume={74},
  pages={933 - 940}
}
Parkinson's disease is a progressive neurodegenerative disorder characterized by selective degeneration of nigrostriatal dopaminergic neurons. Long-term systemic mitochondrial complex I inhibition by rotenone induces selective degeneration of dopaminergic neurons in rats. We have reported dopamine redistribution from vesicles to the cytosol to play a crucial role in selective dopaminergic cell apoptosis. In the present study, we investigated how rotenone causes dopamine redistribution to the… Expand
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References

SHOWING 1-10 OF 57 REFERENCES
Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH-SY5Y Cells
  • M. Watabe, T. Nakaki
  • Biology, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
  • 2007
TLDR
It is demonstrated that rotenone-generated reactive oxygen species are involved in dopamine redistribution to the cytosol, which in turn may play a role in roten one-induced apoptosis of dopaminergic cells. Expand
Rotenone Induces Apoptosis via Activation of Bad in Human Dopaminergic SH-SY5Y Cells
  • M. Watabe, T. Nakaki
  • Biology, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
  • 2004
TLDR
It is demonstrated that Bad activation plays a role in rotenone-induced apoptosis of human dopaminergic SH-SY5Y cells, and the inhibition of caspase-9, which functions downstream from Bad, completely suppressed roten one- induced apoptosis. Expand
Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
TLDR
It is reported that the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), is a selective target for nitration following exposure of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+). Expand
Nitrotyrosine as a marker for peroxynitrite‐induced neurotoxicity: the beginning or the end of the end of dopamine neurons?
TLDR
It is proposed that the dopamine neuronal phenotype can influence the cytotoxic signature of peroxynitrite, and could reveal early steps in drug‐ and disease‐induced damage to the dopamine neuron and form the basis for rational, protective therapies. Expand
Protein Nitration in Parkinson's Disease
TLDR
It is demonstrated here the presence of nitrotyrosine immunoreactivity in Lewy bodies within melanized neurons and in amorphous deposits associated with intact and degenerating neurons, demonstrating that oxidative stress has occurred within the vulnerable neurons of PD. Expand
A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter
TLDR
Taking advantage of selection in MPP+, gene transfer followed by plasmid rescue is used to identify a cDNA clone that encodes a vesicular amine transporter that predicts a novel mammalian protein with 12 transmembrane domains and homology to a class of bacterial drug resistance transporters. Expand
Role of nitric oxide in rotenone‐induced nigro‐striatal injury
TLDR
It is suggested that chronic rotenone administration can lead to significant injury to the nigro‐striatal system, mediated by increased generation of nitric oxide. Expand
Immunochemical Analysis of Vesicular Monoamine Transporter (VMAT2) Protein in Parkinson's Disease
TLDR
Investigating the distribution of VMAT2 in striatum and its loss in PD paralleled that of the dopamine transporter (DAT), a phenotypic marker of dopamine neurons, provides novel and sensitive means for localizing and quantifying VMat2 protein and nigrostriatal dopamine terminals in PD. Expand
Mitochondrial Complex I Inhibitor Rotenone Induces Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species Production*
TLDR
The results suggest that rotenone is able to induce apoptosis via enhancing the amount of mitochondrial reactive oxygen species production. Expand
Positive immunoreactivity for vesicular monoamine transporter 2 in Lewy bodies and Lewy neurites in substantia nigra
TLDR
The involvement of VMAT2 in LBs of the SN suggests the association of this protein in the neurodegeneration of nigral neurons in PD. Expand
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