Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha, Hunan 410125, China.
College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China.
Oxid Med Cell Longev. 2018 Jul 22;2018:1054797. doi: 10.1155/2018/1054797. eCollection 2018.
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.
胎盘在妊娠期间对胎儿发育起着至关重要的作用。胎盘功能障碍可能是由氧化应激引起的，并可能导致胎儿发育异常。因此，预防胎盘氧化应激是确保良好母婴结局的重要措施。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内有效的抗氧化剂。然而，其在胎盘内抗氧化的机制尚不清楚。在本综述中，我们总结了色氨酸、色氨酸代谢物和代谢酶的抗氧化特性研究。讨论了色氨酸抗氧化特性的两种预测机制。（1）色氨酸可在 mTORC1 激活后激活 p62 的磷酸化；磷酸化的 p62 随后使 Nrf2 与 Keap1 解偶联，激活的 Nrf2 进入细胞核诱导抗氧化蛋白的表达，从而提高细胞抗氧化能力。（2）色氨酸犬尿氨酸途径代谢物 3-羟基犬尿氨酸改变 Keap1 的构象，诱导 Nrf2 与 Keap1 解离，激活 Nrf2 进入细胞核并诱导抗氧化蛋白（如 HO-1）的表达，从而增强细胞抗氧化能力。这些机制可能丰富了如何在妊娠期间应用色氨酸作为抗氧化剂的理论，为其在调节妊娠氧化还原状态中的应用提供了技术支持，并丰富了我们对氨基酸营养价值的理解。
