Mechanisms of stress resistance in Snell dwarf mouse fibroblasts: enhanced antioxidant and DNA base excision repair capacity, but no differences in mitochondrial metabolism.
Mechanisms of stress resistance in Snell dwarf mouse fibroblasts: enhanced antioxidant and DNA base excision repair capacity, but no differences in mitochondrial metabolism.
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DOI：
10.1016/j.freeradbiomed.2009.01.014
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发表时间：
2009-04-15
影响因子：
7.4
通讯作者：
Stuart, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Page, Melissa M.;Salmon, Adam B.;Leiser, Scott F.;Robb, Ellen L.;Brown, Melanie F.;Miller, Richard A.;Stuart, Jeffrey A.
关键词：
与正常的同窝鼠相比，长寿命嗅矮鼠的皮肤成纤维细胞可以承受各种氧化和非氧化应激。在这里，我们报告了在不同条件下培养的正常和Snell侏儒小鼠成纤维细胞中细胞内抗氧化和DNA修复酶的水平和活性的差异，包括：3%和20%的环境氧气；血清的存在和缺失；以及外源性氧化应激的加入。在氧气浓度为20%的完全培养基中培养的正常细胞和矮化细胞之间的唯一显著差异是突变细胞中谷胱甘肽过氧化物酶（GPx）活性提高了约40%。在两种基因型中，血清剥夺均引起GPx的增加，但这些活性在矮鼠细胞中仍然较高。缺乏血清和暴露于百草枯或过氧化氢的矮鼠细胞普遍显示过氧化氢酶和DNA碱基切除修复酶的上调。由于这些毒素可以与线粒体相互作用，增加线粒体ROS的产生，我们探索了正常和矮鼠细胞之间的线粒体代谢是否存在差异。然而，线粒体含量和表观线粒体膜电位在基因型之间都没有差异。总的来说，结果表明，较好的过氧化氢代谢和稍强的DNA碱基切除修复能力有助于Snell矮子小鼠成纤维细胞的抗逆性表型。
Dermal fibroblasts from long-lived Snell dwarf mice can withstand a variety of oxidative and non-oxidative stressors compared to normal littermate controls. Here, we report differences in the levels and activities of intracellular antioxidant and DNA repair enzymes between normal and Snell dwarf mice fibroblasts cultured under a variety of conditions, including: 3% and 20% ambient O2; the presence and absence of serum; and the addition of an exogenous oxidative stress. The only significant difference between normal and dwarf cells cultured in complete medium, at 20% O2, was an approximately 40% elevation of glutathione peroxidase (GPx) activity in the mutant cells. Serum deprivation elicited increases in GPx in both genotypes, but these activities remained higher in dwarf mouse cells. Dwarf mouse cells deprived of serum and challenged with exposure to paraquat or hydrogen peroxide showed a generally greater upregulation of catalase and DNA base excision repair enzymes. As these toxins can interact with mitochondria to increase mitochondrial ROS production, we explored whether there were differences in mitochondrial metabolism between normal and dwarf mouse cells. However, neither mitochondrial content nor the apparent mitochondrial membrane potential differed between genotypes. Overall, the results suggest that superior hydrogen peroxide metabolism and a marginally greater DNA base excision repair capacity contribute to the stress resistance phenotype of Snell dwarf mouse fibroblasts.
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