کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1910705 | 1046783 | 2008 | 9 صفحه PDF | دانلود رایگان |
Telomere shortening and redox imbalance have been related to the aging process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc−/−) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc−/− MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc−/− MEF increased catalase expression and activity. TGF-β1 and collagen type IV levels were higher in Terc−/− than in WT MEF. TGF-β1 promoter activity decreased when Terc−/− MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the cause of the TGF-β1 increase. Similar results were obtained in vivo. Homogenized renal cortex from 6-month-old Terc−/− showed higher oxidant capacity, lower catalase activity, greater oxidative damage, and higher TGF-β1 and fibronectin levels than that from WT mice. In summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-β1 and extracellular matrix proteins.
Journal: Free Radical Biology and Medicine - Volume 45, Issue 9, 1 November 2008, Pages 1243–1251