QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mihm, M. J. Articles by Bauer, J. A. Search for Related Content PubMed PubMed Citation Articles by Mihm, M. J. Articles by Bauer, J. A.

 Previous Article  |  Next Article 

The Journal of Neuroscience, 2001, 21:RC149:1-5

RAPID COMMUNICATION
Free 3-Nitrotyrosine Causes Striatal Neurodegeneration In Vivo

Michael J. Mihm, Brandon L. Schanbacher, Benjamin L. Wallace, Lane J. Wallace, Norman J. Uretsky, and John Anthony Bauer

Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210

Peroxynitrite formation has been demonstrated in several neurodegenerative disorders; thus far, protein nitration and consequent alterations in protein function are implicated as mechanistic events. Free 3-nitrotyrosine (free-3NT) is also elevated in these settings; a neurotoxic role for this modified amino acid has not been investigated. We tested the hypothesis that free-3NT is neurotoxic in vivo, using a mouse model of striatal degeneration. The neurodegenerative effects of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) (unilateral intrastriatal injection, 64 nmol) were compared with free-3NT (32 nmol) or free-tyrosine (free-TYR) (32 nmol). 6-OHDA-treated mice exhibited significant ipsilateral turning behavior after D-amphetamine challenge, indicative of unilateral striatal injury (ipsilateral-contralateral turning differential, 21.1 ± 6.8). Significant turning behavior was also observed in free-3NT-treated mice but not in free-tyrosine-treated mice (free-3NT, 16.0 ± 3.9; free-TYR, 1 ± 2.7; p < 0.01). Immunohistochemistry was used to evaluate striatal tyrosine hydroxylase (TH) content. 6-OHDA or free-3NT treatment caused severe reductions in TH immunoreactivity in injected striata compared with the contralateral hemisphere (injected/contralateral immunoreactivity ratio: 6-OHDA, 0.23 ± 0.07; free-3NT, 0.49 ± 0.02). Free-tyrosine treatment had no effect (1.03 ± 0.09). Turning behavior was correlated with striatal TH ratio (p < 0.01). Furthermore, we observed a striking unilateral reduction in TH-positive cell body counts in the substantia nigra pars compacta of 6-OHDA- and free-3NT-treated mice (injected/contralateral cell count ratio: 6-OHDA, 0.40 ± 0.04; free-3NT, 0.59 ± 0.02). Free-tyrosine treatment had no effect (1.05 ± 0.04). No evidence for increased striatal protein incorporation of 3NT was observed in any treatment group. These data represent the first evidence that free-3NT can elicit neurodegenerative effects in vivo; free-3NT may have a causal role in neurodegenerative conditions.

Key words: peroxynitrite; 3-nitrotyrosine; neurodegeneration; Parkinson's disease; nitration; nitric oxide

---

Copyright © Society for Neuroscience  0270-6474//$05.00/0

This article has been cited by other articles:

				A. A. Chaves, R. S. Baliga, M. J. Mihm, B. L. Schanbacher, A. Basuray, C. Liu, A. C. Cook, L. W. Ayers, and J. A. Bauer Bacterial Lipopolysaccharide Enhances Cardiac Dysfunction but Not Retroviral Replication in Murine AIDS: Roles of Macrophage Infiltration and Toll-Like Receptor 4 Expression Am. J. Pathol., March 1, 2006; 168(3): 727 - 735. [Abstract] [Full Text] [PDF]

				Y.-C. T. Huang, Z. Li, L. E. Brighton, J. L. Carson, S. Becker, and J. M. Soukup 3-Nitrotyrosine attenuates respiratory syncytial virus infection in human bronchial epithelial cell line Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L988 - L996. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help