期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 297, 期 3, 页码 C723-C731出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00191.2009
关键词
placental transport; insulin; insulin-like growth factor I; mammalian target of rapamycin
资金
- Swedish Research Council [10838, 14555]
- Swedish Diabetes Association
- Frimurare-Barnhus Direktionen
- Magnus Bergvall Foundation
- Ahlens Foundation
- Wilhelm and Martina Lundgren Foundation
- Anders Otto Sward Foundation
- Royal Society of Arts and Sciences
- Herbert and Karin Jacobsson Foundation
- Royal Swedish Academy of Sciences
Roos S, Lagerlof O, Wennergren M, Powell TL, Jansson T. Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling. Am J Physiol Cell Physiol 297: C723-C731, 2009. First published July 8, 2009; doi:10.1152/ajpcell.00191.2009.-Inhibition of mammalian target of rapamycin (mTOR) signaling in cultured human primary trophoblast cells reduces the activity of key placental amino acid transporters. However, the upstream regulators of placental mTOR are unknown. We hypothesized that glucose, insulin, and IGF-I regulate placental amino acid transporters by inducing changes in mTOR signaling. Primary human trophoblast cells were cultured for 24 h with media containing various glucose concentrations, insulin, or IGF-I, with or without the mTOR inhibitor rapamycin, and, subsequently, the activity of system A, system L, and taurine (TAUT) transporters was measured. Glucose deprivation (0.5 mM glucose) did not significantly affect Thr172-AMP-activated protein kinase phosphorylation or REDD1 expression but decreased S6 kinase 1 phosphorylation at Thr389. The activity of system L decreased in a dose-dependent manner in response to decreasing glucose concentrations. This effect was abolished in the presence of rapamycin. Glucose deprivation had two opposing effects on system A activity: 1) an adaptive upregulation mediated by an mTOR-independent mechanism and 2) downregulation by an mTOR-dependent mechanism. TAUT activity was increased after incubating cells with glucose-deprived media, and this effect was largely independent of mTOR signaling. Insulin and IGF-I increased system A activity and insulin stimulated system L activity, effects that were abolished by rapamycin. We conclude that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta.
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