期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 53, 期 3, 页码 577-588出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.04.010
关键词
Thioredoxin; Oxidative stress; Antioxidants; Apoptosis signaling kinase-1; p38 mitogen-activated protein kinase; Amyloid beta; Retinal degeneration; Free radicals
资金
- Department of Ophthalmology at Georgia Health Sciences University
- Ricerca Finalizzata of the Italian Ministry of Health
- IRCCS Fondazione GB Bietti
Amyloid beta peptides (A beta) have been implicated in the pathogenesis of age-related macular degeneration (ARMD) and glaucoma. In this study, retinas of mice overexpressing A beta (Tg) were compared to those of wild-type mice (Wt) and analyzed for oxidative stress parameters. We observed a progressive decrease in all retinal cell layers, which was significantly greater in Tg mice at 14 months and culminated in loss of the outer retina at 18 months of age. We also observed higher levels of reactive oxygen species, glial fibrillary acidic protein, and hydroperoxide in Tg versus Wt mice (14 months). These effects were associated with phosphorylation/activation of the apoptosis signal kinase 1 and the p38 mitogen-activated kinase. Western blotting analysis revealed progressive increases in the levels of thioredoxin 1 and thioredoxin inhibitory protein in Tg compared to Wt mice. No changes were observed in the levels of thioredoxin reductase 1 (TrxR1): however, measurements of TrxR1 activity showed a 42.7 +/- 8% reduction in Tg mice versus Wt at 14 months of age. Our data suggest that A beta-mediated retinal neurotoxicity involves impairment of the thioredoxin system and enhanced oxidative stress, potentially implicating this mechanism in the pathogenesis of ARMD and glaucoma. (C) 2012 Elsevier Inc. All rights reserved.
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