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Publication : Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice.

First Author  Jishage K Year  2001
Journal  J Biol Chem Volume  276
Issue  3 Pages  1669-72
PubMed ID  11076932 Mgi Jnum  J:67046
Mgi Id  MGI:1929784 Doi  10.1074/jbc.C000676200
Citation  Jishage K, et al. (2001) Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice. J Biol Chem 276(3):1669-72
abstractText  Alpha-tocopherol transfer protein (alpha-TTP), a cytosolic protein that specifically binds alpha-tocopherol, is known as a product of the causative gene in patients with ataxia that is associated with vitamin E deficiency. Targeted disruption of the alpha-TTP gene revealed that alpha-tocopherol concentration in the circulation was regulated by alpha-TTP expression levels. Male alpha-TTP(-/-) mice were fertile; however, placentas of pregnant alpha-TTP(-/-) females were severely impaired with marked reduction of labyrinthine trophoblasts, and the embryos died at mid-gestation even when fertilized eggs of alpha-TTP(+/+) mice were transferred into alpha-TTP(-/-) recipients. The use of excess alpha-tocopherol or a synthetic antioxidant (BO-653) dietary supplement by alpha-TTP(-/-) females prevented placental failure and allowed full-term pregnancies. In alpha-TTP(+/+) animals, alpha-TTP gene expression was observed in the uterus, and its level transiently increased after implantation (4.5 days postcoitum). Our results suggest that oxidative stress in the labyrinth region of the placenta is protected by vitamin E during development and that in addition to the hepatic alpha-TTP, which governs plasma alpha-tocopherol level, the uterine alpha-TTP may also play an important role in supplying this vitamin.
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