کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1910316 1046764 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Age-associated oxidative damage to the p62 promoter: implications for Alzheimer disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Age-associated oxidative damage to the p62 promoter: implications for Alzheimer disease
چکیده انگلیسی

The absence of the p62 gene in mouse brain leads to biochemical and cognitive deficits that resemble Alzheimer disease (AD). In this context, the objective of this study was to examine the relationship between age-induced oxidative damage to the p62 promoter and AD. Increased 8-OHdG staining, a marker of oxidative stress, was observed in brain sections from mice deficient in the p62 gene compared to control. Treatment of MEF cells deficient in p62 with H2O2 resulted in decreased cell survival and an absence of Nrf2 nuclear translocation. The mouse p62 promoter exhibited elevated oxidative damage with increasing age, and the degree of p62 promoter damage was also age-correlated in human brain samples. In human subjects, the expression of p62 was decreased in AD brain relative to age-matched controls, and likewise decreased p62 expression correlated with oxidative damage to the promoter. Treatment of HEK cells with H2O2 resulted in decreased p62 expression concomitant with increased promoter damage. Consistent with these findings, a transgenic AD mouse model also exhibited increased p62 promoter damage and reduced p62 levels in brain. Altogether, our results reveal that oxidative damage to the p62 promoter correlates with decreased expression of p62 and may contribute to age-associated neurodegenerative disease such as AD and others.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 46, Issue 4, 15 February 2009, Pages 492–501
نویسندگان
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