Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root
Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root
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DOI：
10.1016/s0891-5849(03)00462-3
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发表时间：
2003-11-01
影响因子：
7.4
通讯作者：
Paigen, B
中科院分区：
文献类型：
--
作者：
Phelan, SA;Wang, X;Paigen, B
哺乳动物1-Cys过氧化物氧还蛋白（Prdx6）是能够保护细胞免受金属催化的氧化损伤的过氧化物氧还蛋白家族的独特成员。我们最近确定Prdx6作为数量性状基因座Ath1的候选基因，Ath1是一种负责小鼠饮食诱导的动脉粥样硬化易感性差异的基因。为了研究Prdx6在动脉粥样硬化中的作用，我们在Ath1敏感的C57BL/6J背景下产生了过表达来自Ath1抗性129/SvJ品系的Prdx6等位基因的转基因小鼠。这些小鼠在多个组织中表达了显著升高的Prdx6 mRNA和蛋白水平，包括肝脏、主动脉和腹腔巨噬细胞，这些组织积累了显著较低水平的过氧化氢，揭示了这些小鼠增强的抗氧化活性。然而，过度表达。Prdx6的表达在体外对LDL氧化没有保护作用，喂食致动脉粥样硬化饮食10周的转基因小鼠对动脉粥样硬化的抵抗力没有增加，也没有维持与Ath1抵抗表型一致的高饮食前血浆HDL水平。此外，Prdx6等位基因从敏感菌株被证明有更高的抗氧化活性比抗性菌株。这些数据表明，在转基因小鼠中，由于Prdx6过表达而增加的过氧化物酶活性不足以保护小鼠免受动脉粥样硬化，并且Prdx6不太可能是Ath1的潜在基因。(C)2003年爱思唯尔公司
The mammalian 1-Cys peroxiredoxin (Prdx6) is a unique member of the peroxiredoxin family of proteins capable of protecting cells from metal-catalyzed oxidative damage. We recently identified Prdx6 as a candidate for the quantitative trait locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis susceptibility in mice. To investigate the role of Prdx6 in atherosclerosis, we generated transgenic mice that overexpress the Prdx6 allele from the Ath1-resistant 129/SvJ strain on an Ath1-susceptible C57BL/6J background. These mice expressed significantly elevated levels of Prdx6 mRNA and protein in multiple tissues including liver, aorta, and peritoneal macrophages, which accumulated significantly lower levels of hydrogen peroxide, revealing an enhanced antioxidant activity in these mice. However, overexpression. of Prdx6 had no protective effect on LDL oxidation in vitro, and transgenic mice fed an atherogenic diet for 10 weeks did not possess an increased resistance to atherosclerosis nor did they maintain the high prediet plasma HDL levels consistent with the Ath1-resistant' phenotype. In addition, the Prdx6 allele from the susceptible strain was shown to have a higher antioxidant activity than that of the resistant strains. These data suggest that the increased peroxidase activity attributable to Prdx6 overexpression in transgenic mice is not sufficient to protect mice from atherosclerosis, and that Prdx6 is not likely to be the gene underlying Ath1. (C) 2003 Elsevier Inc.