کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1906356 1046283 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cellular senescence determines endothelial cell damage induced by uremia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Cellular senescence determines endothelial cell damage induced by uremia
چکیده انگلیسی


• Senescent HUVEC have high sensitivity to uremia compared with young cells.
• Endothelial damage induced by uremia is related with the increased oxidative stress.
• In both HUVEC and rats model, vit C prevent endothelial apoptosis.
• Vit C did not decrease the oxidative stress associated to replicative senescence.

Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells.Human umbilical vein endothelial cells (HUVEC) was incubated with human uremic serum and, in the animal model, endothelial cells were obtained from aortas of uremic and no uremic rats. Vitamin C was used to prevent oxidative stress. Senescence, assessed by telomere length and enzyme-betagalactosidase (β-gal), reactive oxygen species (ROS), mitochondrial depolarization (JC-1 probe), caspase 3, and apoptosis were determined by flow cytometry. NF-κB activity was determined by Western blot.Uremic serum increased ROS and NF-κB in young and aging HUVEC. However only in aging cells, uremic serum induced apoptosis (vs young HUVEC, p < 0.01). The endothelial damage induced by uremia seems to be related with the increased oxidative stress, since in both HUVEC and in the experimental model of renal disease in rats, vitamin C prevents endothelial apoptosis. However, vitamin C did not decrease the oxidative stress associated to senescence. These results showed that as compared with young cells, senescent cells have high sensitivity to damage associated to the oxidative stress induced by the uremia. Consequently, protecting senescent endothelial cells from increased oxidative stress might be an effective therapeutic approach in the treatment of vascular disorders in chronic kidney diseases.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 48, Issue 8, August 2013, Pages 766–773
نویسندگان
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