The United Graduate School of Agricultural Sciences, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan.
Graduate School of Sustainability Science, Tottori University, 4-101 Koyama-Minami, Tottori City, Tottori, 680-8553, Japan.
Redox Biol. 2020 Oct;37:101724. doi: 10.1016/j.redox.2020.101724. Epub 2020 Sep 15.
Using Caenorhabditis elegans as a model animal, we evaluated the effects of chronical supplementation with high-dose folic acid on physiological events such as life cycle and egg-laying capacity and folate metabolism. Supplementation of high-dose folic acid significantly reduced egg-laying capacity. The treated worms contained a substantial amount of unmetabolized folic acid and exhibited a significant downregulation of the mRNAs of cobalamin-dependent methionine synthase reductase and 5,10-methylenetetrahydrofolate reductase. In vitro experiments showed that folic acid significantly inhibited the activity of cobalamin-dependent methionine synthase involved in the metabolism of both folate and methionine. In turn, these metabolic disorders induced the accumulation of unmetabolized homocysteine, leading to severe oxidative stress in worms. These results were similar to the phenomena observed in mammals during folate deficiency.
我们使用秀丽隐杆线虫作为模式动物，评估了长期补充高剂量叶酸对生命周期和产卵能力等生理事件以及叶酸代谢的影响。高剂量叶酸的补充显著降低了产卵能力。处理过的线虫含有大量未代谢的叶酸，并表现出钴胺素依赖性蛋氨酸合成酶还原酶和 5,10-亚甲基四氢叶酸还原酶的 mRNA 显著下调。体外实验表明，叶酸显著抑制了参与叶酸和蛋氨酸代谢的钴胺素依赖性蛋氨酸合成酶的活性。反过来，这些代谢紊乱导致未代谢的同型半胱氨酸积累，从而导致线虫严重的氧化应激。这些结果与哺乳动物叶酸缺乏时观察到的现象相似。
