Telomerase deficiency promotes oxidative stress by reducing catalase activity.
Free Radic Biol Med
; 45(9): 1243-51, 2008 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-18718525
ABSTRACT
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-beta1 and collagen type IV levels were higher in Terc(-/-) than in WT MEF. TGF-beta1 promoter activity decreased when Terc(-/-) MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the cause of the TGF-beta1 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-beta1 and fibronectin levels than that from WT mice. In summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-beta1 and extracellular matrix proteins.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catalase
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Fator de Crescimento Transformador beta
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Estresse Oxidativo
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Telomerase
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article