Telomerase deficiency promotes oxidative stress by reducing catalase activity.
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.
Pérez-Rivero
Gema
G
Departamento Fisiología, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Ruiz-Torres
María P
MP
Díez-Marqués
María L
ML
Canela
Andrés
A
López-Novoa
José M
JM
Rodríguez-Puyol
Manuel
M
Blasco
María A
MA
Rodríguez-Puyol
Diego
D
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*
D016212:Transforming Growth Factor beta; D002374:Catalase; D019098:Telomerase