Deficiency of ascorbic acid decreases the contents of tetrahydrobiopterin in the liver and the brain of ODS rats.
Deficiency of ascorbic acid decreases the contents of tetrahydrobiopterin in the liver and the brain of ODS rats.
复制标题
抗坏血酸缺乏会降低 ODS 大鼠肝脏和大脑中四氢生物蝶呤的含量。
DOI：
10.1016/j.neulet.2019.134656
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Takeshita;N.;Kawade;N.;Suzuki;W.;Hara;S.;Horio;F. and Ichinose;H.
四氢生物蝶呤 (BH4) 是酪氨酸羟化酶和色氨酸羟化酶的辅助因子，酪氨酸羟化酶和色氨酸羟化酶是多巴胺、去甲肾上腺素和血清素生物合成的必需酶。众所周知，BH4 是一种不稳定的分子，很容易被氧化。由于抗坏血酸 (AsA) 是一种大脑中富含的抗氧化剂，因此大脑中 AsA 浓度的改变可能会影响 BH4 的正常代谢。在这里，我们使用 ODS 大鼠检查了 AsA 缺乏对 BH4 浓度的影响，这些大鼠的 AsA 合成基因有缺陷。与饲喂含有足量 AsA 的基础饮食的动物相比，ODS 大鼠摄入缺乏 AsA 的饮食 2 周后，肝脏中的 AsA 水平大幅降低了 7%，大脑中的 AsA 水平降低了 55%。与饲喂基础饮食的大鼠相比，饲喂无 AsA 饮食的 ODS 大鼠肝脏中的 BH4 浓度下降至 71%，脑中的 BH4 浓度下降至 88%。我们发现，与喂食基础饮食的 ODS 大鼠相比，多巴胺、去甲肾上腺素和血清素的水平也有所下降。我们的数据表明，AsA 缺乏会影响肝脏和大脑中的 BH4 浓度，导致大脑中的单胺水平降低。这些结果表明 AsA 通过改变 BH4 代谢在神经精神和心血管疾病的病理生理学中发挥着重要作用。
Tetrahydrobiopterin (BH4) is a cofactor for tyrosine hydroxylase and tryptophan hydroxylase, which are essential enzymes for the biosynthesis of dopamine, norepinephrine, and serotonin. It has been known that BH4 is a labile molecule and easily oxidized. As ascorbic acid (AsA) is an antioxidant that is rich in the brain, alteration in the AsA concentration in the brain may affect the proper metabolism of BH4. Here, we examined the effect of AsA deficiency on the concentration of BH4 using ODS rats, which are defective in the gene for AsA synthesis. Intake of an AsA-deficient diet for 2 weeks in ODS rats resulted in great reductions in the AsA levels up to 7 % in the liver and up to 55 % in the brain compared to animals fed a basal diet containing an adequate amount of AsA. The BH4 concentrations in ODS rats fed an AsA-free diet were decreased to 71 % in the liver and 88 % in the brain of those fed a basal diet. We found that the levels of dopamine, norepinephrine, and serotonin were also decreased compared with the ODS rats fed a basal diet. Our data showed that AsA deficiency can affect the BH4 concentrations in the liver and brain, resulting in decreases in the monoamine levels in the brain. These results suggest the importance of AsA in the pathophysiology of neuropsychiatric and cardiovascular disorders through alteration in the BH4 metabolism.