Low ascorbic acid and increased oxidative stress in gulo(-/-) mice during development.
Low ascorbic acid and increased oxidative stress in gulo(-/-) mice during development.
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DOI：
10.1016/j.brainres.2010.06.037
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发表时间：
2010-08-19
期刊：
影响因子：
2.9
通讯作者：
May, James M.
中科院分区：
文献类型：
--
作者：
Harrison, Fiona E.;Meredith, M. Elizabeth;Dawes, Sean M.;Saskowski, Jeanette L.;May, James M.
产前和产后发育过程中维生素 C（抗坏血酸，AA）的消耗会导致发育中的大脑和其他器官产生氧化应激。这种损害可能会对以后的大脑功能产生不可逆转的影响。我们研究了无法合成自身抗坏血酸的古洛糖酸内酯氧化酶 (gulo) 基因敲除小鼠发育过程中 AA 缺乏与氧化应激之间的关系。杂合 gulo(+/-) 小鼠可以合成 AA，并且通常具有与野生型小鼠相似的组织水平。 Gulo(+/-) 水坝与 gulo(+/-) 雄性交配以产生每种可能基因型的后代。总体而言，胚胎第 20 天 (E20) 和产后第 1 天 (P1) 幼崽在怀孕期间通过充足的 AA 转移可免受氧化应激。出生后第 10 天 (P10) gulo (−/−) 小鼠肝脏和小脑中的 AA 水平显着降低，丙二醛 (MDA) 水平显着升高。在出生后第 18 天的幼鼠 (P18) 中，gulo(−/−) 小鼠的 AA 水平进一步下降，并且在肝脏中的 MDA 和皮质中的 F2-异前列腺素中观察到伴随的氧化应激升高。此外，gulo(−/−)小鼠皮层、小脑和肝脏的总谷胱甘肽水平较高，表明补偿性抗氧化系统被激活。这些数据显示 gulo(−/−) 小鼠的 AA 水平和氧化应激之间存在直接关系。它们强化了抗坏血酸在预防动物发育中的大脑氧化应激方面的关键作用，因为动物（如人类）无法合成自己的 AA。
Vitamin C (ascorbic acid, AA) depletion during pre-natal and post-natal development can lead to oxidative stress in the developing brains and other organs. Such damage may lead to irreversible effects on later brain function. We studied the relationship between AA deficiency and oxidative stress during development in gulonolactone oxidase (gulo) knockout mice that are unable to synthesize their own ascorbic acid. Heterozygous gulo(+/−) mice can synthesize AA and typically have similar tissue levels to wild-type mice. Gulo(+/−) dams were mated with gulo(+/−) males to provide offspring of each possible genotype. Overall, embryonic day 20 (E20) and post-natal day 1 (P1) pups were protected against oxidative stress by sufficient AA transfer during pregnancy. On post-natal day 10 (P10) AA levels were dramatically lower in liver and cerebellum in gulo (−/−) mice and malondialdehyde (MDA) levels were significantly increased. In post-natal day 18 pups (P18) AA levels decreased further in gulo(−/−) mice and oxidative stress was observed in the accompanying elevations in MDA in liver, and F2-isoprostanes in cortex. Further, total glutathione levels were higher in gulo(−/−) mice in cortex, cerebellum and liver, indicating that a compensatory antioxidant system was activated. These data show a direct relationship between AA level and oxidative stress in the gulo(−/−) mice. They reinforce the critical role of ascorbic acid in preventing oxidative stress in the developing brain in animals that, like humans, cannot synthesize their own AA.
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影响因子：
2.5
作者：
Aksenov, MY;Markesbery, WR
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