Hypoxia-induced regulation of placental REDD1 and mTOR was impaired in a rat model of estrogen-induced cholestasis.
Arch Gynecol Obstet
; 294(6): 1219-1226, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27549090
PURPOSE: Hypoxia inducible factor-1α (HIF-1α), regulated in development and DNA damage response-1 (REDD1), and mammalian target of rapamycin (mTOR) play distinct roles in response to hypoxia. The aim of this study was to evaluate whether the HIF-1α-REDD1-mTOR-mediated hypoxic stress response also operates normally in estrogen-induced cholestasis. METHODS: Pregnant rats were administered with ethinylestradiol (EE) to induce cholestasis and then were subjected to feto-placental ischemia reperfusion (IR); as controls, one group received neither EE nor IR, and another two groups received only EE or IR. RESULTS: Giving rats either EE alone or IR alone increased placental levels of HIF-1α, REDD1, glucose transporter-1 (GLUT1), and phosphoglycerate kinase-1 (PGK1), and decreased placental mTOR and lactic dehydrogenase A (LDHA) expression compared with the control rats. Subjecting EE-treated rats to IR did not further alter placental levels of REDD1 or mTOR, while it did elevate placental HIF-1α, GLUT1, and PGK1 expression, and decline LDHA expression. By contrast, mRNA levels did not differ significantly among the four groups for any of the proteins analyzed. CONCLUSIONS: This study manifested that placental HIF-1α and its downstream glucose metabolism effectors can effectively react to hypoxia in EE-induced cholestasis rats. However, hypoxia-induced REDD1 and mTOR alternation, which responds efficiently in normal placentas, was impaired in EE-induced cholestasis placentas.
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Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Fatores de Transcrição
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Colestase
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Serina-Treonina Quinases TOR
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article