Reduction of mitochondrial H2O2 by overexpressing peroxiredoxin 3 improves glucose tolerance in mice.
Reduction of mitochondrial H2O2 by overexpressing peroxiredoxin 3 improves glucose tolerance in mice.
复制标题
通过过表达过氧蛋白3来降低线粒体H2O2，可提高小鼠的葡萄糖耐受性。
DOI：
10.1111/j.1474-9726.2008.00432.x
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发表时间：
2008-12
期刊：
影响因子：
7.8
通讯作者：
Ran Q
中科院分区：
文献类型：
--
作者：
Chen L;Na R;Gu M;Salmon AB;Liu Y;Liang H;Qi W;Van Remmen H;Richardson A;Ran Q
H2 O2是线粒体产生的主要活性氧物质，在衰老和糖尿病等疾病的发病机制中起重要作用;然而，线粒体H2 O2的细胞和生理作用仍然知之甚少。Peroxiredoxin 3（Prdx 3/Prx 3）是一种位于线粒体中的硫氧还蛋白过氧化物酶。为了了解线粒体H2 O2在衰老和年龄相关疾病发病机制中的细胞和生理作用，我们产生了过表达Prdx 3的转基因小鼠（Tg（PRDX 3）小鼠）。Tg（PRDX 3）小鼠在广泛的组织中过表达Prdx 3，并且Prdx 3表达仅定位于线粒体中。由于Prdx 3表达增加，来自Tg（PRDX 3）小鼠的线粒体产生显著减少量的H2 O2，并且来自Tg（PRDX 3）小鼠的细胞对应激诱导的细胞死亡和凋亡具有增加的抗性。有趣的是，Tg（PRDX 3）小鼠显示出改善的葡萄糖稳态，如通过其降低的血糖水平和增加的葡萄糖清除率所证明的。Tg（PRDX 3）小鼠也被保护免于由高脂肪饮食喂养诱导的高血糖症和葡萄糖耐受不良。我们的研究结果进一步表明，GSK 3的抑制可能在介导Tg（PRDX 3）小鼠的葡萄糖耐量表型改善中发挥作用。因此，我们的研究结果表明，通过过表达Prdx 3减少线粒体H2 O2可改善葡萄糖耐量。
H2O2 is a major reactive oxygen species produced by mitochondria that is implicated to be important in aging and pathogenesis of diseases such as diabetes; however, the cellular and physiological roles of mitochondrial H2O2 remain poorly understood. Peroxiredoxin 3 (Prdx3/Prx3) is a thioredoxin peroxidase localized in mitochondria. To understand the cellular and physiological roles of mitochondrial H2O2 in aging and pathogenesis of age-associated diseases, we generated transgenic mice overexpressing Prdx3 (Tg(PRDX3) mice). Tg(PRDX3) mice overexpress Prdx3 in a broad range of tissues, and the Prdx3 expression is localized exclusively in the mitochondria. As a result of increased Prdx3 expression, mitochondria from Tg(PRDX3) mice produce significantly reduced amount of H2O2, and cells from Tg(PRDX3) mice have increased resistance to stress-induced cell death and apoptosis. Interestingly, Tg(PRDX3) mice show improved glucose homeostasis, as evidenced by their reduced levels of blood glucose and increased glucose clearance. Tg(PRDX3) mice are also protected against hyperglycemia and glucose intolerance induced by high-fat diet feeding. Our results further show that the inhibition of GSK3 may play a role in mediating the improved glucose tolerance phenotype in Tg(PRDX3) mice. Thus, our results indicate that reduction of mitochondrial H2O2 by overexpressing Prdx3 improves glucose tolerance.
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影响因子：
4.8
作者：
Groen, A;Lemeer, S;den Hertog, J
通讯作者：
den Hertog, J
DOI：
10.1016/0925-4439(95)00024-x
发表时间：
1995-05-24
影响因子：
6.2
作者：
AMES, BN;SHIGENAGA, MK;HAGEN, TM
通讯作者：
HAGEN, TM
影响因子：
4.1
作者：
Bayne, ACV;Mockett, RJ;Sohal, RS
通讯作者：
Sohal, RS
影响因子：
64.8
作者：
Houstis, N;Rosen, ED;Lander, ES
通讯作者：
Lander, ES
影响因子：
4.7
作者：
Hattori, F;Murayama, N;Oikawa, S
通讯作者：
Oikawa, S