The Tryptophan Pathway Targeting Antioxidant Capacity in the Placenta.

The Tryptophan Pathway Targeting Antioxidant Capacity in the Placenta.
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针对胎盘抗氧化能力的色氨酸途径

DOI:
10.1155/2018/1054797
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发表时间:
2018
影响因子:
--
通讯作者:
Fu C
Fu C
中科院分区:
生物学2区
文献类型:
--
作者:
Xu K;Liu G;Fu C

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胎盘在怀孕期间对胎儿发育起着至关重要的作用。胎盘功能障碍可由氧化应激引起,并可导致胎儿发育异常。因此,预防胎盘的氧化应激是确保积极分娩结果的重要措施。研究表明,色氨酸及其代谢产物可以有效地清除自由基(包括活性氧和活性氯)。因此,色氨酸及其代谢产物被认为是胎盘中有效的抗氧化剂。然而,胎盘中这些抗氧化特性的机制仍然未知。本文综述了色氨酸、色氨酸代谢物和代谢酶的抗氧化特性。色氨酸的抗氧化性能的两个预测机制进行了讨论。(1)mTORC 1激活后,色氨酸可激活p62的磷酸化,磷酸化的p62解偶联Nrf 2与Keap 1的相互作用,激活的Nrf 2进入细胞核,诱导抗氧化蛋白的表达,从而提高细胞的抗氧化能力。(2)色氨酸犬尿氨酸途径代谢产物3-羟基邻氨基苯甲酸改变Keap 1的构象,诱导Nrf 2和Keap 1解离,激活Nrf 2进入细胞核,诱导抗氧化蛋白(如HO-1)表达,从而增强细胞抗氧化能力。这些机制可能丰富了如何在怀孕期间应用色氨酸作为抗氧化剂的理论,为其用于调节怀孕的氧化还原状态提供技术支持,并丰富了我们对氨基酸营养价值的理解。
The placenta plays a vital role in fetal development during pregnancy. Dysfunction of the placenta can be caused by oxidative stress and can lead to abnormal fetal development. Preventing oxidative stress of the placenta is thus an important measure to ensure positive birth outcomes. Research shows that tryptophan and its metabolites can efficiently clean free radicals (including the reactive oxygen species and activated chlorine). Consequently, tryptophan and its metabolites are suggested to act as potent antioxidants in the placenta. However, the mechanism of these antioxidant properties in the placenta is still unknown. In this review, we summarize research on the antioxidant properties of tryptophan, tryptophan metabolites, and metabolic enzymes. Two predicted mechanisms of tryptophan's antioxidant properties are discussed. (1) Tryptophan could activate the phosphorylation of p62 after the activation of mTORC1; phosphorylated p62 then uncouples the interaction between Nrf2 and Keap1, and activated Nrf2 enters the nucleus to induce expressions of antioxidant proteins, thus improving cellular antioxidation. (2) 3-Hydroxyanthranilic acid, a tryptophan kynurenine pathway metabolite, changes conformation of Keap1, inducing the dissociation of Nrf2 and Keap1, activating Nrf2 to enter the nucleus and induce expressions of antioxidant proteins (such as HO-1), thereby enhancing cellular antioxidant capacity. These mechanisms may enrich the theory of how to apply tryptophan as an antioxidant during pregnancy, providing technical support for its use in regulating the pregnancy's redox status and enriching our understanding of amino acids' nutritional value.
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