کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8326915 | 1540197 | 2018 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SIRT1 reverses senescence via enhancing autophagy and attenuates oxidative stress-induced apoptosis through promoting p53 degradation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Stem cell senescence and exhaustion are considered important drivers of organismal aging, and human adipose-derived stem cells (ADSCs) have emerged as a promising cell source for cell-based therapy. However, aging and low survival rate compromise the optimal outcome of cell-based therapy due to oxidative stress in the graft areas. Oxidative stress has long been considered to be harmful to cells, nevertheless, in this study, we found that lower concentration of hydrogen peroxide (H2O2) decreased the number of SA-βgal-immunopositive cells, which was ameliorated by inhibition of SIRT1. Autophagy, a degradation mechanism that plays a major role in maintaining cellular homeostasis and, is involved in this effect. SIRT1 protein level in ADSCs was increased by the treatment with H2O2, meanwhile, H2O2 activated p53-depended apoptosis in high concentration. Incubation of ADSCs with H2O2 dose dependently induced ADSCs apoptosis. SIRT1 overexpression reduced the rate of ADSCs apoptosis, whereas SIRT1 downregulation and EX527 displayed the opposite effect. SIRT1 overexpression decreased the total p53 protein, whereas SIRT1 downregulation and EX527 increased the amount of p53 protein. Co-immunoprecipitation assay showed that SIRT1 could bind to p53, reduce its acetylation level, and treatment with nutlin-3A reversed the effect of SIRT1 on the level of p53 in ADSCs. These results suggest that SIRT1 had a pivotally protective role in the regulation of ADSCs aging and apoptosis induced by H2O2.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 117, 1 October 2018, Pages 225-234
Journal: International Journal of Biological Macromolecules - Volume 117, 1 October 2018, Pages 225-234
نویسندگان
Tao Liu, Xiaorong Ma, Tianxiang Ouyang, Huiping Chen, Jun Lin, Jun Liu, Yan Xiao, Jie Yu, Yingying Huang,