title: Impact of indoleamine 2,3-dioxygenase on the antioxidant system in the placentas of severely pre-eclamptic patients.
abstract: 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.
authors: Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. nharuki@fujita-hu.ac.jp
authors: Haruki
authors: H
authors: Nishizawa
authors: Machiko
authors: M
authors: Suzuki
authors: Kanako
authors: K
authors: Pryor-Koishi
authors: Takao
authors: T
authors: Sekiya
authors: Shin
authors: S
authors: Tada
authors: Hiroki
authors: H
authors: Kurahashi
authors: Yasuhiro
authors: Y
authors: Udagawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000502:physiology*; D018384:Oxidative Stress; D010920:Placenta / Q000201:enzymology* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000201:enzymology* / Q000209:etiology; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D000975:Antioxidants; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine