Telomerase deficiency promotes oxidative stress by reducing catalase activity

Free Radical Biology & Medicine
Gema Pérez-RiveroD Rodríguez-Puyol

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.

Citations

Dec 5, 2009·Antioxidants & Redox Signaling·Nicole BüchnerJudith Haendeler
Jul 22, 2014·The International Journal of Biochemistry & Cell Biology·Maria del NogalMaría P Ruiz-Torres
Mar 21, 2012·The International Journal of Biochemistry & Cell Biology·Marta González-RamosDiego Rodríguez-Puyol
Feb 11, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hamid SaeedMoustapha Kassem
Jul 27, 2011·Biochemical Society Transactions·Marisa IborraBelén Beltrán
Jul 26, 2014·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Laila Abou-Zeid, Hany N Baraka
Jul 9, 2016·The European Respiratory Journal·Amparo EscribanoFrancisco Dasí
Jul 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carlos SebastiánAntonio Celada
Oct 23, 2017·Redox Biology·José Santiago Ibáñez-CabellosFederico V Pallardó
Apr 17, 2021·Medicina clínica·Hanane BouarichDiego Rodríguez Puyol

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