Positive Regulation of Decidualization by l-Type Amino Acid Transporter 1 (lat1) in Pregnant Mice

Wang, Xiaojie; Tan, Dongmei; Ma, Jing; Liang, Hao; Zhang, Qian; Tan, Yi; Wang, Jiang; Luo, Wei

doi:10.3390/nu8110704

Cited by 11 publications

(7 citation statements)

References 35 publications

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“…In the present study, the basal expression of Lat1 , Oatp4a1 , and Snat4 transporters was significantly reduced at GD 18 compared with that at GD 13, whereas the expression of the remaining transporters did not change. Expression of Lat1 mRNA in Kun‐Ming mouse placenta was significantly higher at GD 12 than at GD 16 and 18, 29 in agreement with Lat1 expression observed in this study. However, in human placenta, LAT1 expression was increased in late gestation, and Oatp4a1 expression was similar across gestation 21 .…”

Section: Discussionsupporting

confidence: 91%

Effect of levetiracetam on the gene expression of placental transporters in a murine model

et al. 2022

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Objective Levetiracetam (LEV) is an antiseizure medication prescribed to women during childbearing age. The impact of LEV on placental transporters is poorly understood. This study aimed to assess the effect of LEV exposure on the messenger RNA (mRNA) expression of placental transporters for hormones and nutrients and to correlate their expression with the drug's serum concentration in pregnant mice. Methods Studies were conducted on gestational days (GD) 13 and 18, following oral treatment with 100 mg/kg LEV or the vehicle every 24 h after weaning. Serum LEV measurements were performed by High‐performance liquid chromatography with a UV detector (HPLC‐UV). The weight, height, and width of the fetuses were also analyzed. In addition, the placental expression of transporters xCt, Lat1, Oatp4a1, Fr‐α, Rfc, and Snat4 was evaluated through semi‐quantitative real‐time polymerase chain reaction (qPCR). The Kruskal‐Wallis and the Mann‐Whitney U tests were used to determine the statistical significance (p < .05). The correlation between serum LEV concentration and placental gene expression was evaluated using the Spearman test. Results The weight, height, and width were lower in the fetuses exposed to LEV compared with the control group (p < .05). The number of fetuses was lower in the LEV‐exposed group than in the control GD 13 group (p < .001). No significant differences were detected in the mRNA expression level at GD 13. At GD 18, the expression of Lat1, Oatp4a1, xCT, and Snat4 was higher in the group treated with LEV compared with the control group (p < .05), whereas the expression of Rfc was lower (p < .05). No correlation was identified between serum LEV concentrations and gene expression levels. Significance The repression of the Rfc transcript by LEV at GD 18 suggests that the protein expression would be abolished contributing to the observed intrauterine growth restriction (IUGR). Furthermore, the significant increase in mRNA of xCt, Snat4, Oatp4a1, and Lat1 might be a compensatory mechanism for fetal survival at GD 18.

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Section: Discussionsupporting

confidence: 91%

Effect of levetiracetam on the gene expression of placental transporters in a murine model

et al. 2022

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“…We have also shown that hTCs show higher LAT1 protein levels than HPECs, suggesting that LAT1 may be of greater importance for amino acid transport into STB than into fetal endothelial cells. In line with this, a role for LAT1 in proper placentation [45] and STB development [46] has been previously demonstrated.…”

Section: Lat1 Is Required For Mehg Uptake But Also For Protection Frosupporting

confidence: 70%

Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

Widhalm

Forsthuber

Ellinger

et al. 2021

IJMS

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The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

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“…Human trophoblasts have also been shown to express LAT1 to a greater extent than human placental endothelial cells. The role of LAT1 in placentation [ 149 ] and cytotrophoblast development [ 150 ] was demonstrated earlier.…”

Section: Participation Of Lat1 and Lat2 In Various Physiological Proc...mentioning

confidence: 98%

Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers

Khavinson

Linkova

Kozhevnikova

et al. 2022

IJMS

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Ultrashort peptides (USPs), consisting of 2–7 amino-acid residues, are a group of signaling molecules that regulate gene expression and protein synthesis under normal conditions in various diseases and ageing. USPs serve as a basis for the development of drugs with a targeted mechanism of action. The purpose of this review is to systematize the available data on USP transport involving POT and LAT transporters in various organs and tissues under normal, pathological and ageing conditions. The carriers of the POT family (PEPT1, PEPT2, PHT1, PHT2) transport predominantly di- and tripeptides into the cell. Methods of molecular modeling and physicochemistry have demonstrated the ability of LAT1 to transfer not only amino acids but also some di- and tripeptides into the cell and out of it. LAT1 and 2 are involved in the regulation of the antioxidant, endocrine, immune and nervous systems’ functions. Analysis of the above data allows us to conclude that, depending on their structure, di- and tripeptides can be transported into the cells of various tissues by POT and LAT transporters. This mechanism is likely to underlie the tissue specificity of peptides, their geroprotective action and effectiveness in the case of neuroimmunoendocrine system disorders.

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Positive Regulation of Decidualization by l-Type Amino Acid Transporter 1 (lat1) in Pregnant Mice

Cited by 11 publications

References 35 publications

Effect of levetiracetam on the gene expression of placental transporters in a murine model

Effect of levetiracetam on the gene expression of placental transporters in a murine model

Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers

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