Uric acid enhances longevity and endurance and protects the brain against ischemia
Uric acid enhances longevity and endurance and protects the brain against ischemia
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DOI：
10.1016/j.neurobiolaging.2018.10.031
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发表时间：
2019-03-01
影响因子：
4.2
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
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作者：
Cutler, Roy G.;Camandola, Simonetta;Mattson, Mark P.
在哺乳动物中，血清尿酸（UA）水平与寿命呈正相关。人类具有高水平的UA，因为他们缺乏存在于寿命较短的哺乳动物中的功能性尿酸氧化酶（UOX）。在这里，我们发现，雄性和雌性小鼠与UOX单倍不足表现出年龄相关的尿酸水平升高，而不是雄性UOX+/-小鼠的寿命显着增加野生型小鼠相比。UOX+/-小鼠的血清UA水平在跑步机运动后升高，但野生型小鼠没有，UOX+/-小鼠的耐力显著高于野生型小鼠。在局灶性缺血性中风模型中，UOX+/-小鼠表现出脑源性神经营养因子水平升高、脑损伤减轻和功能结局改善。在代谢和氧化应激条件下（在肌肉和脑缺血的情况下运行），UOX+/-小鼠的肌肉和脑组织中的氧化蛋白硝化和脂质过氧化水平降低，与之前的证据一致，即UA可以消除过氧亚硝酸盐和羟基自由基。我们的研究结果揭示了UA在寿命决定，耐力和脑损伤的适应性反应中的作用，并提出了保护细胞免受损伤和优化身体表现的新方法。爱思唯尔公司出版
Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/- mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/- mice, but not wild-type mice, and the endurance of the UOX+/- mice is significantly greater than wild-type mice. UOX+/- mice exhibit elevated levels of brain-derived neurotrophic factor, reduced brain damage and improved functional outcome in a model of focal ischemic stroke. Levels of oxidative protein nitration and lipid peroxidation are reduced in muscle and brain tissues of UOX+/- mice under conditions of metabolic and oxidative stress (running in the case of muscle and ischemia in the case of the brain), consistent with prior evidence that UA can scavenge peroxynitrite and hydroxyl radical. Our findings reveal roles for UA in life span determination, endurance and adaptive responses to brain injury, and suggest novel approaches for protecting cells against injury and for optimizing physical performance. Published by Elsevier Inc.