Regulation of placental amino acid transporter activity by mammalian target of rapamycin

Roos, Sara; Kanai, Yoshikatsu; Prasad, Puttur D.; Powell, Theresa L.; Jansson, Thomas

doi:10.1152/ajpcell.00330.2008

Cited by 130 publications

(147 citation statements)

References 69 publications

(77 reference statements)

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“…It is well established that mTOR functions as a nutrient sensor, and we have previously demonstrated that this signaling pathway is a positive regulator of placental amino acid transport ( 21,22 ). Because oleic acid has been reported to activate mTOR signaling in HepG2 cells ( 29 ), mTOR is a potential mediator of oleic acid-stimulated amino acid transport.…”

Section: Silencing Tlr4 Prevents Oleic Acid Stimulation Of System a Amentioning

confidence: 85%

“…This protocol has been widely used and validated, and results in the isolation of cells that are expressing cytokeratin 7, a syncytial marker, that do not express vimentin, and that undergo biochemical differentiation as measured by hCG release ( 21,27,32,33 ). The cells were plated on 6-well plates at a density of 1.5 × 10 6 per well (for and p38 mitogen-activated protein kinase (MAPK).…”

Section: Isolation and Maintenance Of Trophoblast Cellsmentioning

confidence: 99%

“…The mole cular mechanisms regulating placental amino acid transporters involve multiple signaling pathways ( 20 ). We have previously shown in cultured human primary trophoblast cells that the mammalian target of rapamycin (mTOR) signaling pathway is a positive regulator of system A and system L amino acid transporter activities ( 21 ). Furthermore, placental mTOR signaling is reduced in cases of fetal growth restriction ( 22 ).…”

Section: Isolation and Maintenance Of Trophoblast Cellsmentioning

confidence: 99%

“…Primer design: forward, 5 ′ -TTTGGACAGTTTCCCACATTGA-3 ′ ; reverse, 5 ′ -AAGCATTCC CACCTTTGTTGG-3 ′ . Succinate dehydrogenase complex, subunit A (SDHA) and TATA box binding protein (TBP) were selected as housekeeping genes, with primers designed according to a previously published report ( 21 ). All samples were analyzed in at least duplicates.…”

Section: Quantifi Cation Of Tlr4 Mrna Expressionmentioning

confidence: 99%

“…Measuring activity of system A and system L amino acid transporters was performed as previously reported ( 21 ). System A transporter activity was measured as sodium-dependent 14 C-methylaminoisobutyric acid (MeAIB) uptake, and system L transporter activity by 2-amino-2norbornanecarboxylic acid (BCH)-inhibitable uptake of 3 H-leucine.…”

Section: Measurement Of Amino Acid Uptakementioning

confidence: 99%

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Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4

Lager

Gaccioli

Ramirez

et al. 2013

Journal of Lipid Research

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Section: Silencing Tlr4 Prevents Oleic Acid Stimulation Of System a Amentioning

confidence: 85%

Section: Isolation and Maintenance Of Trophoblast Cellsmentioning

confidence: 99%

Section: Isolation and Maintenance Of Trophoblast Cellsmentioning

confidence: 99%

Section: Quantifi Cation Of Tlr4 Mrna Expressionmentioning

confidence: 99%

Section: Measurement Of Amino Acid Uptakementioning

confidence: 99%

See 3 more Smart Citations

Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4

Lager

Gaccioli

Ramirez

et al. 2013

Journal of Lipid Research

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Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Zhang

2015

Journal Cellular Physiology

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Synthetic glucocorticoids (GCs) such as dexamethasone (Dex) are widely given to pregnant women to induce maturation and improve viability of preterm infants. Despite the beneficial effects, synthetic GCs have adverse effects on placental growth and nutrient transport system. However, the molecular mechanisms involved in these events remain unknown. Here we use a human placental choriocarcinoma cell line (BeWo) as model to explore the pathway linking amino acids transport with cell viability under Dex challenge. BeWo cells treated with Dex (100 nM) for 24 h demonstrated G1/S cell cycle arrest together with enhanced autophagy and apoptosis. Concurrently, the amino acid carrier SLC7A5 was down-regulated in association with impaired cellular amino acids uptake and inhibition of mammalian target of rapamycin (mTOR) signaling. Similar cellular responses were observed in BeWo cells treated with BCH, a classical System L inhibitor which inactivates SLC7A5. The glucocorticoid receptor (GR) antagonist RU486 was able to diminish Dex-induced translocation of GR into nucleus and to abolish these effects. Furthermore, Dex treatment significantly promoted the binding of GR to the proximal promoter sequence of SLC7A5 gene. Taken together, our results show that Dex downregulates SLC7A5 expression via GR-mediated transrepression. The impaired amino acids uptake leads to inhibition of mTOR signaling which in turn causes inhibited proliferation and enhanced autophagy and apoptosis in BeWo cells. These findings indicate that SLC7A5 mediates the effect of Dex on cell viability, thus providing a novel molecular target for the prevention and treatment of Dex-induced cell cycle arrest and apoptosis in placental cells.

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Prenatal high‐fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat

Song

Sun

Boersma

et al. 2017

Obesity

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Objective: This study aimed to determine how the rat placenta and fetus respond to maternal high-fat (HF) diet during gestation and to identify the possible mechanisms. Methods: Pregnant Sprague-Dawley rats were fed with standard chow (13.5% fat) or HF (60% fat) diet during gestation. Placentas were collected on gestation day 21. Results: HF dams had greater fat mass, higher plasma leptin, lower plasma adiponectin, and impaired glucose tolerance during pregnancy. The placental labyrinth thickness was reduced in both male and female fetuses of HF dams. In HF male placentas, glucose transporter 3 gene expression, system A amino acid transporter (SNAT) 2 gene expression, and SNAT2 protein expression were increased through the activation of the mTORC1 4EBP1 branch. In HF female placentas, gene expression of insulin-like growth factor 2 (IGF2) and IGF2 receptor was elevated compared to placentas of females fed standard chow. Although male and female placentas responded differently to prenatal HF diet exposure, both male and female fetal weight was not altered by maternal HF diet. Conclusions: Placenta responds and adapts to maternal metabolic changes by altering placental layer thickness, mTORC1 signaling, expression of nutrient transporters, and growth factors in a sex-specific manner.Obesity (2017) 25, 909-919.

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Regulation of placental amino acid transporter activity by mammalian target of rapamycin

Abstract: Roos S, Kanai Y, Prasad PD, Powell TL, Jansson T. Regulation of placental amino acid transporter activity by mammalian target of rapamycin.

Cited by 130 publications

References 69 publications

Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4

Oleic acid stimulates system A amino acid transport in primary human trophoblast cells mediated by toll-like receptor 4

Dexamethasone Downregulates SLC7A5 Expression and Promotes Cell Cycle Arrest, Autophagy and Apoptosis in BeWo Cells

Prenatal high‐fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat

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