Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

摘要: Inhibition of mammalian target rapamycin (mTOR) signaling in cultured human primary trophoblast cells reduces the activity key placental amino acid transporters. However, upstream regulators mTOR are unknown. We hypothesized that glucose, insulin, and IGF-I regulate transporters by inducing changes signaling. Primary were for 24 h with media containing various glucose concentrations, or IGF-I, without inhibitor rapamycin, and, subsequently, system A, L, taurine (TAUT) was measured. Glucose deprivation (0.5 mM glucose) did not significantly affect Thr172-AMP-activated protein kinase phosphorylation REDD1 expression but decreased S6 1 at Thr389. The L a dose-dependent manner response to decreasing concentrations. This effect abolished presence rapamycin. had two opposing effects on A activity: 1) an "adaptive" upregulation mediated mTOR-independent mechanism 2) downregulation mTOR-dependent mechanism. TAUT increased after incubating glucose-deprived media, this largely independent Insulin insulin stimulated activity, conclude pathway represents important intracellular regulatory link between nutrient growth factor concentrations transport placenta.