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Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.


ABSTRACT: INTRODUCTION:Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. METHODS:Placental tissue was collected from healthy, term pregnancies (n = 15 no-labor; n = 12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NF?B p65 and PPAR? DNA binding activity was measured in isolated nuclei. RESULTS:Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NF?B and PPAR? DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. DISCUSSION AND CONCLUSION:Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor.

SUBMITTER: Lager S 

PROVIDER: S-EPMC4270912 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Labor inhibits placental mechanistic target of rapamycin complex 1 signaling.

Lager S S   Aye I L M H IL   Gaccioli F F   Ramirez V I VI   Jansson T T   Powell T L TL  

Placenta 20141018 12


<h4>Introduction</h4>Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport  ...[more]

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