| Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. | |
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MedLine Citation:
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PMID: 10329595 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson's disease (PD). To investigate the extent and distribution of nucleic acid oxidative damage in these vulnerable dopaminergic neurons, we immunohistochemically characterized a common product of nucleic acid oxidation, 8-hydroxyguanosine (8OHG). In PD patients, cytoplasmic 8OHG immunoreactivity was intense in neurons of the SN, and present to a lesser extent in neurons of the nucleus raphe dorsalis and oculomotor nucleus, and occasionally in glia. The proportion of 8OHG immunoreactive SN neurons was significantly greater in PD patients compared to age-matched controls. Midbrain sections from patients with multiple system atrophy-Parkinsonian type (MSA-P) and dementia with Lewy bodies (DLB) also were examined. These showed increased cytoplasmic 8OHG immunoreactivity in SN neurons in both MSA-P and DLB compared to controls; however, the proportion of positive neurons was significantly less than in PD patients. The regional distribution of 8OHG immunoreactive neurons within the SN corresponded to the distribution of neurodegeneration for these three diseases. Nuclear 8OHG immunoreactivity was not observed in any individual. The type of cytoplasmic nucleic acid responsible for 8OHG immunoreactivity was analyzed by preincubating midbrain sections from PD patients with RNase, DNase, or both enzymes. 8OHG immunoreactivity was substantially diminished by either RNase or DNase, and completely ablated by both enzymes. These results suggest that oxidative damage to cytoplasmic nucleic acid is selectively increased in midbrain, especially the SN, of PD patients and much less so in MSA-P and DLB patients. Moreover, oxidative damage to nucleic acid is largely restricted to cytoplasm with both RNA and mitochondrial DNA as targets. |
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Authors:
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J Zhang; G Perry; M A Smith; D Robertson; S J Olson; D G Graham; T J Montine |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of pathology Volume: 154 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 1999 May |
Date Detail:
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Created Date: 1999-06-03 Completed Date: 1999-06-03 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1423-9 Citation Subset: AIM; IM; S |
Affiliation:
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Departments of Pathology, Medicine, and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. jing.zhang@mcmail.vanderbilt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Cell Death Cytoplasm / genetics DNA / metabolism* Female Guanosine / analogs & derivatives, metabolism Humans Hydroxyl Radical Immunohistochemistry Male Neurons / metabolism*, ultrastructure Oxidative Stress / physiology* Parkinson Disease / metabolism* RNA / metabolism* Substantia Nigra / cytology, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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ES05842/ES/NIEHS NIH HHS; HL56693/HL/NHLBI NIH HHS; NS33460/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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118-00-3/Guanosine; 3352-57-6/Hydroxyl Radical; 3868-31-3/8-hydroxyguanosine; 63231-63-0/RNA; 9007-49-2/DNA |
| Comments/Corrections | |
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