Spontaneous hypomorphic mutations in antioxidant enzymes of mice
Spontaneous hypomorphic mutations in antioxidant enzymes of mice
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DOI：
10.1016/j.freeradbiomed.2003.09.017
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发表时间：
2003-12-15
影响因子：
7.4
通讯作者：
Mori, M
中科院分区：
文献类型：
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作者：
Guo, ZJ;Higuchi, K;Mori, M
抗氧化酶系统是有氧动物最小化活性氧引起的损伤的关键。抗氧化酶活性改变的自发突变动物应有助于研究这些酶在体内的功能。我们研究了10个近交系小鼠主要抗氧化酶基因的核苷酸序列，包括过氧化氢酶（Cat），超氧化物歧化酶（Sod 1，Sod 2，Sod 3），谷胱甘肽过氧化物酶（Gpx 1，Gpx 2，Gpx 3，Gpx 4，Gpx 5）和谷胱甘肽还原酶（Gsr）。非同义核苷酸多态性在所有的基因，除了Gpx 1，Gpx 3和Gpx 4。值得注意的是，SJL/J小鼠品系在Gsr和Sod 2基因中具有独特的核苷酸取代，这分别导致GSR和SOD 2中的Asp 39 Ala和Val 138 Met氨基酸取代。SJL/J小鼠的GSR比活性降低到NZB/N小鼠的65%。然而，体内活性在SJL/J中较高，这是由于该酶的表达上调。SJL/J小鼠的SOD 2活性降低至其他小鼠品系的一半。与这种减少一致，线粒体中的氧化损伤增加，如通过总谷胱甘肽的减少和蛋白质氧化水平的增加所证明的。这些自发的亚型等位基因在自由基生物学的研究中将是有价值的。(C)2003年爱思唯尔公司
An antioxidant enzymatic system is pivotal for aerobic animals to minimize the damage induced by reactive oxygen species. Spontaneous mutant animals with altered antioxidant enzyme activity should be useful for the study of the function of these enzymes in vivo. We examined the nucleotide sequences of the genes for the major antioxidant enzymes, including catalase (Cat), superoxide dismutase (Sod1, Sod2, Sod3), glutathione peroxidase (Gpx1, Gpx2, Gpx3, Gpx4, Gpx5), and glutathione reductase (Gsr) in 10 inbred mouse strains. Nonsynonymous nucleotide polymorphisms were identified in all genes, except for Gpx1, Gpx3, and Gpx4. Notably, the SJL/J mouse strain possessed unique nucleotide substitutions in the Gsr and Sod2 genes, which led to Asp39Ala and Val138Met amino acid substitutions in GSR and SOD2, respectively. The specific activity of GSR of SJL/J mice was reduced to 65% of that of NZB/N mice. In vivo activity, however, was higher in SJL/J, due to upregulated expression of the enzyme. The SOD2 activity in SJL/J mice was reduced to half that of other mouse strains. Consistent with this reduction, oxidative damage in the mitochondria was increased as demonstrated by a decrease of total glutathione and an increase in the levels of protein oxidation. These spontaneous hypomorphic alleles would be valuable in the study of free radical biology. (C) 2003 Elsevier Inc.