Abstract |
Biliverdin reductase-A (BVR-A) is a pleiotropic enzyme and plays pivotal role in the antioxidant defense against free radicals as well as in cell homeostasis. Together with heme oxygenase, BVR-A forms a powerful system involved in the cell stress response during neurodegenerative disorders including Alzheimer's disease (AD), whereas due to the serine/ threonine/ tyrosine kinase activity the enzyme regulates glucose metabolism and cell proliferation. In this paper, we report results that demonstrate BVR-A undergoes post-translational oxidative and nitrosative modifications in the hippocampus, but not cerebellum, of subjects with AD and amnestic mild cognitive impairment (MCI). A significant increase of nitrated BVR-A was demonstrated only in AD and MCI hippocampi, whereas no significant modifications were found in cerebellar tissue. In addition, a significant reduction in protein carbonyl-derivatives of BVR-A was found in both AD and MCI hippocampi (15% and 18%, respectively). Biliverdin reductase-bound 4-hydroxynonenals were not modified in hippocampi and cerebella from AD and MCI subjects. These results supported the hypothesis of a prevalence of nitrosative stress-induced modifications on BVR-A structure, and this evidence was confirmed by a significant upregulation of inducible nitric oxide synthase in hippocampal tissue of subjects with AD and MCI that was not present in cerebellum. In conclusion, nitrosative stress-induced modifications on hippocampal BVR-A are an early event in the pathogenesis of AD since they appear also in MCI subjects and could contribute to the antioxidant and metabolic derangement characteristic of these neurodegenerative disorders.
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Authors | Eugenio Barone, Fabio Di Domenico, Giovanna Cenini, Rukhsana Sultana, Raffaella Coccia, Paolo Preziosi, Marzia Perluigi, Cesare Mancuso, D Allan Butterfield |
Journal | Journal of Alzheimer's disease : JAD
(J Alzheimers Dis)
Vol. 25
Issue 4
Pg. 623-33
( 2011)
ISSN: 1875-8908 [Electronic] Netherlands |
PMID | 21483094
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aldehydes
- Reactive Nitrogen Species
- 3-nitrotyrosine
- Tyrosine
- Nitric Oxide Synthase Type II
- Heme Oxygenase (Decyclizing)
- Oxidoreductases Acting on CH-CH Group Donors
- biliverdin reductase
- 4-hydroxy-2-nonenal
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Topics |
- Aged
- Aged, 80 and over
- Aldehydes
(metabolism)
- Alzheimer Disease
(enzymology, metabolism)
- Blotting, Western
- Brain
(enzymology, metabolism)
- Cerebellum
(metabolism)
- Cognitive Dysfunction
(enzymology, metabolism)
- Female
- Heme Oxygenase (Decyclizing)
(metabolism)
- Hippocampus
(metabolism)
- Homeostasis
- Humans
- Immunoprecipitation
- Male
- Nitric Oxide Synthase Type II
(genetics, metabolism)
- Oxidative Stress
- Oxidoreductases Acting on CH-CH Group Donors
(metabolism)
- Protein Carbonylation
(physiology)
- Reactive Nitrogen Species
(metabolism)
- Tyrosine
(analogs & derivatives, metabolism)
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