| Metabolism of 3-nitrotyrosine induces apoptotic death in dopaminergic cells. | |
| | |
MedLine Citation:
|
PMID: 16763020 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Intrastriatal injection of 3-nitrotyrosine, which is a biomarker for nitrating oxidants, provokes dopaminergic neuronal death in rats by unknown mechanisms. Herein, we show that extracellular 3-nitrotyrosine is transported via the l-aromatic amino acid transporter in nondopaminergic NT2 cells, whereas in dopaminergic PC12 cells, it is transported by both the l-aromatic amino acid and the dopamine transporters. In both cell lines, 3-nitrotyrosine is a substrate for tyrosine tubulin ligase, resulting in its incorporation into the C terminus of alpha-tubulin. In NT2 cells, incorporation of 3-nitrotyrosine into alpha-tubulin induces a progressive, reversible reorganization of the microtubule architecture. In PC12 cells, 3-nitrotyrosine decreases intracellular dopamine levels and is metabolized by the concerted action of the aromatic amino acid decarboxylase and monoamine oxidase. Intracellular levels of 133 micromol of 3-nitrotyrosine per mole of tyrosine did not alter NT2 viability but induced PC12 apoptosis. The cell death was reversed by caspases and aromatic amino acid decarboxylase and monoamine oxidase inhibitors. 3-Nitrotyrosine induced loss of tyrosine hydroxylase-positive primary rat neurons, which was also prevented by an aromatic amino acid decarboxylase inhibitor. These findings provide a novel mechanism by which products generated by reactive nitrogen species induce dopaminergic neuron death and thus may contribute to the selective neurodegeneration in Parkinson's disease. |
| | |
Authors:
|
Béatrice Blanchard-Fillion; Delphine Prou; Manuela Polydoro; David Spielberg; Elpida Tsika; Zeneng Wang; Stanley L Hazen; Michael Koval; Serge Przedborski; Harry Ischiropoulos |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 26 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2006 Jun |
Date Detail:
|
Created Date: 2006-06-09 Completed Date: 2006-07-07 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
|
Languages: eng Pagination: 6124-30 Citation Subset: IM |
Affiliation:
|
Stokes Research Institute, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Transport Systems
/
metabolism Animals Apoptosis / physiology* Aromatic-L-Amino-Acid Decarboxylases / metabolism Cell Death Cell Line, Tumor Cell Physiological Phenomena* Cell Survival Cells / metabolism* Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / metabolism Humans Mesencephalon / cytology Microtubules / ultrastructure Monoamine Oxidase / metabolism Neurons / physiology Nitrophenols / metabolism PC12 Cells Phenylacetates Rats Tubulin / metabolism Tyrosine / analogs & derivatives*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
AG13966/AG/NIA NIH HHS; HL076491/HL/NHLBI NIH HHS; HL54926/HL/NHLBI NIH HHS; NS38370/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amino Acid Transport Systems; 0/Dopamine Plasma Membrane Transport Proteins; 0/Nitrophenols; 0/Phenylacetates; 0/Tubulin; 10463-20-4/4-hydroxy-5-nitrophenyl acetic acid; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; EC 1.4.3.4/Monoamine Oxidase; EC 4.1.1.28/Aromatic-L-Amino-Acid Decarboxylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Minimizing polymorphic metabolism in drug discovery: evaluation of the utility of in vitro methods f...
Next Document: Vasopressin inhibits glutamate release via two distinct modes in the brainstem.