Expression and regulation of 4F2hc and hLAT1  in human trophoblasts

The neutral amino acid transport system L is a sodium-independent transport system in human placenta and choriocarcinoma cells. Recently, it was found that the heterodimer composed of hLAT1 (a light-chain protein) and 4F2 heavy chain (4F2hc), a type II transmembrane glycoprotein, is responsible for system L amino acid transport. We found that the mRNAs of 4F2hc and hLAT1 were expressed in the human placenta and a human choriocarcinoma cell line. The levels of the 4F2hc and hLAT1 proteins in the human placenta increased at full term compared with those at midtrimester. Immunohistochemical data showed that these proteins were localized mainly in the placental apical membrane. Data from leucine uptake experiments, Northern blot analysis, and immunoblot analysis showed that this transport system was partially regulated by protein kinase C and calcium ionophore in the human choriocarcinoma cell line. Our results suggest that the heterodimer of 4F2hc and hLAT1 may play an important role in placental amino acid transport system L.

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Modulation of the activity of amino acid transport system L by phorbol esters and calmodulin antagonists in a human placental choriocarcinoma cell line

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/0167-4889(92)90255-a ◽

1992 ◽

Vol 1136 (2) ◽

pp. 181-188 ◽

Cited By ~ 25

Author(s):

Sammanda Ramamoorthy ◽

Frederick H. Leibach ◽

Virendra B. Mahesh ◽

Vadivel Ganapathy

Keyword(s):

Amino Acid ◽

Cell Line ◽

Transport System ◽

Amino Acid Transport ◽

Phorbol Esters ◽

Acid Transport ◽

Calmodulin Antagonists ◽

Amino Acid Transport System ◽

System L ◽

Choriocarcinoma Cell Line

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Expression and adaptive regulation of amino acid transport system A in a placental cell line under amino acid restriction

Reproduction ◽

10.1530/rep.1.00808 ◽

2006 ◽

Vol 131 (5) ◽

pp. 951-960 ◽

Cited By ~ 40

Author(s):

H N Jones ◽

C J Ashworth ◽

K R Page ◽

H J McArdle

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Cell Line ◽

Transport System ◽

Amino Acid Transport ◽

Essential Amino Acids ◽

Acid Transport ◽

Amino Acid Transport System ◽

Transcellular Transport ◽

System A

Trans-placental transport of amino acids is vital for the developing fetus. Using the BeWo cell line as a placental model, we investigated the effect of restricting amino acid availability on amino acid transport system type A. BeWo cells were cultured either in amino acid-depleted (without non-essential amino acids) or control media for 1, 3, 5 or 6 h. System A function was analysed using α(methyl-amino)isobutyric acid (MeAIB) transcellular transport studies. Transporter (sodium coupled neutral amino acid transporter (SNAT1/2)) expression was analysed at mRNA and protein level by Northern and Western blotting respectively. Localisation was carried out using immunocytochemistry. MeAIB transcellular transport was significantly (P< 0.05) increased by incubation of the cells in amino acid-depleted medium for 1 h, and longer incubation times caused further increases in the rate of transfer. However, the initial response was not accompanied by an increase in SNAT2 mRNA; this occurred only after 3 h and further increased for the rest of the 6-h incubation. Similarly, it took several hours for a significant increase in SNAT2 protein expression. In contrast, relocalisation of existing SNAT2 transporters occurred within 30 min of amino acid restriction and continued throughout the 6-h incubation. When the cells were incubated in medium with even lower amino acid levels (without non-essential plus 0.5 × essential amino acids), SNAT2 mRNA levels showed further significant (P< 0.0001) up-regulation. However, incubation of cells in depleted medium for 6 h caused a significant (P= 0.014) decrease in the expression of SNAT1 mRNA. System L type amino acid transporter 2 (LAT2) expression was not changed by amino acid restriction, indicating that the responses seen in the system A transporters were not a general cell response. These data have shown that placental cells adaptin vitroto nutritional stress and have identified the physiological, biochemical and genomic mechanisms involved.

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