Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Syst Biol Reprod Med. 2011 Aug;57(4):174-8. doi: 10.3109/19396368.2011.587590. Epub 2011 Jul 1.
Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme of the kynurenine pathway that degrades L-tryptophan, but a wider range of functions have now been proposed for this enzyme, including antioxidant activity. Our previous study revealed that reduced IDO expression in the placenta induces defective feto-maternal immuno-tolerance leading to the onset of pre-eclampsia. In our present study, we assessed the effects of low placental IDO activity as an antioxidant. The placental levels of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a maker for oxidative damage to DNA, were significantly higher in pre-eclamptic than normotensive pregnancies (P<0.05). Immunohistochemical signals of 8-OHdG were detected mainly in syncytiotrophoblasts and vascular endothelial cells, and co-localized with those for IDO. Furthermore, a significant inverse correlation was found between the IDO activity and 8-OhdG levels. These results show that oxidative stress is associated with decreased IDO activity in the pre-eclamptic placenta and suggest an impact of low IDO activity other than immune modulation in promoting the onset of this disorder.
色氨酸 2,3-双加氧酶（IDO）是犬尿氨酸途径的限速酶，可降解 L-色氨酸，但现在已经提出了这种酶的更广泛的功能，包括抗氧化活性。我们之前的研究表明，胎盘内 IDO 表达减少会导致胎儿-母体免疫耐受缺陷，从而引发子痫前期。在我们目前的研究中，我们评估了低胎盘 IDO 活性作为抗氧化剂的作用。与正常血压妊娠相比，子痫前期患者胎盘的 8-羟基-2'-脱氧鸟苷（8-OHdG）水平明显升高（P<0.05）。8-OHdG 的免疫组化信号主要在合体滋养层细胞和血管内皮细胞中检测到，并与 IDO 的信号共定位。此外，还发现 IDO 活性与 8-OhdG 水平之间存在显著的负相关。这些结果表明，氧化应激与子痫前期胎盘内 IDO 活性降低有关，并提示低 IDO 活性除了免疫调节外，还可能会影响这种疾病的发生。
