Correlation of mitochondrial superoxide dismutase and DNA polymerase β in mammalian dermal fibroblasts with species maximal lifespan
Correlation of mitochondrial superoxide dismutase and DNA polymerase β in mammalian dermal fibroblasts with species maximal lifespan
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DOI：
10.1016/j.mad.2007.10.004
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发表时间：
2007-11-01
影响因子：
5.3
通讯作者：
Stuart, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Brown, Melanie F.;Stuart, Jeffrey A.
真核细胞已经进化出复杂的机制，以在面临有氧代谢反应副产物的慢性攻击时保持其基因组材料的保真度。这些机制包括抗氧化剂和DNA修复酶。长寿哺乳动物物种的皮肤成纤维细胞比那些寿命较短的物种更能抵抗氧化应激[Kapahi，P.，Boulton，M.E.，柯克伍德，T. B.，1999.哺乳动物寿命与细胞抗应激能力呈正相关。Free Radic. Biol. Med. 26，495 -500]，我们推测这是由于寿命较长的物种具有更强的抗氧化剂和/或DNA修复能力。我们使用最大寿命在5至122年之间的哺乳动物物种的真皮成纤维细胞来测试这一假设。成纤维细胞在18或3%O-2下培养。在抗氧化酶中，只有锰超氧化物歧化酶与最长寿命呈正相关（p < 0.01）。DNA的氧化损伤主要通过碱基切除修复（BER）途径修复。BER酶活性显示与供体物种MLS（聚合酶β）无相关性（脱嘌呤/脱嘧啶核酸内切酶）或负相关（p < 0.01）。标准培养条件（18%O-2）诱导抗氧化剂和BER酶的活性，这表明广泛采用的“正常”细胞培养条件是不适当的高氧，这可能会混淆文化中的细胞氧化应激反应的研究的解释。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Eukaryotic cells have evolved elaborate mechanisms to preserve the fidelity of their genomic material in the face of chronic attack by reactive byproducts of aerobic metabolism. These mechanisms include antioxidant and DNA repair enzymes. Skin fibroblasts of long-lived mammalian species are more resistant to oxidative stress than those of shorter-lived species [Kapahi, P., Boulton, M.E., Kirkwood, T.B., 1999. Positive correlation between mammalian life span and cellular resistance to stress. Free Radic. Biol. Med. 26,495-500], and we speculated that this is due to greater antioxidant and/or DNA repair capacities in longer-lived species. We tested this hypothesis using dermal fibroblasts from mammalian species with maximum lifespans between 5 and 122 years. The fibroblasts were cultured at either 18 or 3% O-2. Of the antioxidant enzymes only manganese superoxide dismutase was found to positively correlate with maximum lifespan (p < 0.01). Oxidative damage to DNA is primary repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation (apurinic/apyrimidinic endonuclease), or correlated negatively (p < 0.01) with donor species MLS (polymerase beta). Standard culture conditions (18% O-2) induced both antioxidant and BER enzymes activities, suggesting that the 'normal' cell culture conditions widely employed are inappropriately hyperoxic, which likely confounds the interpretation of studies of cellular oxidative stress responses in culture. (c) 2007 Elsevier Ireland Ltd. All rights reserved.