کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1908682 1046679 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Loss of thioredoxin function in retinas of mice overexpressing amyloid β
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Loss of thioredoxin function in retinas of mice overexpressing amyloid β
چکیده انگلیسی

Amyloid β peptides (Aβ) have been implicated in the pathogenesis of age-related macular degeneration (ARMD) and glaucoma. In this study, retinas of mice overexpressing Aβ (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 Aβ-mediated retinal neurotoxicity involves impairment of the thioredoxin system and enhanced oxidative stress, potentially implicating this mechanism in the pathogenesis of ARMD and glaucoma.


► TrxS impairment is associated with Aβ-induced retinal tissue injury.
► Retinas of mice over-expressing Aβ have increased oxidative stress and ASK1/p38MAPK activation.
► Retinas of mice over-expressing Aβ have decreased TrxR1 activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 53, Issue 3, 1 August 2012, Pages 577–588
نویسندگان
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