title: Telomerase deficiency promotes oxidative stress by reducing catalase activity.
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.
authors: Departamento Fisiología, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
authors: Gema
authors: G
authors: Pérez-Rivero
authors: María P
authors: MP
authors: Ruiz-Torres
authors: María L
authors: ML
authors: Díez-Marqués
authors: Andrés
authors: A
authors: Canela
authors: José M
authors: JM
authors: López-Novoa
authors: Manuel
authors: M
authors: Rodríguez-Puyol
authors: María A
authors: MA
authors: Blasco
authors: Diego
authors: D
authors: Rodríguez-Puyol
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D018384:Oxidative Stress; D019098:Telomerase / Q000172:deficiency* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D002374:Catalase; D019098:Telomerase