Pérez-Rivero Gema, Ruiz-Torres María P, Díez-Marqués María L, Canela Andrés, López-Novoa José M, Rodríguez-Puyol Manuel, Blasco María A, Rodríguez-Puyol Diego
Departamento Fisiología, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Free Radic Biol Med. 2008 Nov 1;45(9):1243-51. doi: 10.1016/j.freeradbiomed.2008.07.017. Epub 2008 Jul 30.
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.
端粒缩短和氧化还原失衡与衰老过程有关。我们使用从缺乏端粒酶活性（Terc(-/-)）的小鼠中分离出的培养小鼠胚胎成纤维细胞（MEF）来分析氧化还原平衡以及端粒酶缺乏所引发的功能后果。与野生型（WT）MEF相比，Terc(-/-) MEF具有更大的氧化损伤，表现为超氧阴离子和过氧化氢产生量更高，而过氧化氢酶活性更低。在Terc(-/-) MEF中恢复端粒酶活性可增加过氧化氢酶的表达和活性。Terc(-/-)中TGF-β1和IV型胶原水平高于WT MEF。当Terc(-/-) MEF与外源性过氧化氢酶孵育时，TGF-β1启动子活性降低，这表明过氧化氢酶缺乏是TGF-β1增加的原因。在体内也获得了类似的结果。6个月大的Terc(-/-)小鼠的肾皮质匀浆比WT小鼠的肾皮质匀浆表现出更高的氧化能力、更低的过氧化氢酶活性、更大的氧化损伤以及更高的TGF-β1和纤连蛋白水平。总之，端粒酶缺乏会降低过氧化氢酶活性，导致氧化还原失衡，进而促进TGF-β1和细胞外基质蛋白的过度表达。
