Jang Youngmok C, Pérez Viviana I, Song Wook, Lustgarten Michael S, Salmon Adam B, Mele James, Qi Wenbo, Liu Yuhong, Liang Hanyu, Chaudhuri Asish, Ikeno Yuji, Epstein Charles J, Van Remmen Holly, Richardson Arlan
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78245-3207, USA.
J Gerontol A Biol Sci Med Sci. 2009 Nov;64(11):1114-25. doi: 10.1093/gerona/glp100. Epub 2009 Jul 24.
Genetic manipulations of Mn superoxide dismutase (MnSOD), SOD2 expression have demonstrated that altering the level of MnSOD activity is critical for cellular function and life span in invertebrates. In mammals, Sod2 homozygous knockout mice die shortly after birth, and alterations of MnSOD levels are correlated with changes in oxidative damage and in the generation of mitochondrial reactive oxygen species. In this study, we directly tested the effects of overexpressing MnSOD in young (4-6 months) and old (26-28 months) mice on mitochondrial function, levels of oxidative damage or stress, life span, and end-of-life pathology. Our data show that an approximately twofold overexpression of MnSOD throughout life in mice resulted in decreased lipid peroxidation, increased resistance against paraquat-induced oxidative stress, and decreased age-related decline in mitochondrial ATP production. However, this change in MnSOD expression did not alter either life span or age-related pathology.
对锰超氧化物歧化酶（MnSOD，即SOD2）表达进行的基因操作表明，改变MnSOD活性水平对无脊椎动物的细胞功能和寿命至关重要。在哺乳动物中，Sod2纯合敲除小鼠出生后不久即死亡，MnSOD水平的改变与氧化损伤及线粒体活性氧生成的变化相关。在本研究中，我们直接测试了在年轻（4 - 6个月）和年老（26 - 28个月）小鼠中过表达MnSOD对线粒体功能、氧化损伤或应激水平、寿命以及临终病理的影响。我们的数据表明，小鼠一生中MnSOD约两倍的过表达导致脂质过氧化减少、对百草枯诱导的氧化应激的抵抗力增加，以及与年龄相关的线粒体ATP生成下降减少。然而，MnSOD表达的这种变化并未改变寿命或与年龄相关的病理状况。
