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Analysis of the effects of polyunsaturated fatty acids on transporter expressions using a PCR array: Induction of xCT/SLC7A11 in human placental BeWo cells.

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Title: Analysis of the effects of polyunsaturated fatty acids on transporter expressions using a PCR array: Induction of xCT/SLC7A11 in human placental BeWo cells.
Authors: Ono, Kanako Browse this author
Furugen, Ayako Browse this author →KAKEN DB
Kurosawa, Yuko Browse this author
Jinno, Naoko Browse this author
Narumi, Katsuya Browse this author →KAKEN DB
Kobayashi, Masaki Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Keywords: Arachidonic acid (AA)
Docosahexaenoic acid (DHA)
Eicosapentaenoic acid (EPA)
Placenta; Transporter
xCT/SLC7A11
Issue Date: Jan-2019
Journal Title: Placenta
Volume: 75
Start Page: 34
End Page: 41
Publisher DOI: 10.1016/j.placenta.2018.11.010
PMID: 30712664
Abstract: OBJECTIVE: Polyunsaturated fatty acids (PUFAs), including arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are essential for adequate fetal growth. The aim of the present study was to elucidate the effects of PUFAs on the expression and function of placental transporters, which play important roles in placental functions including the supply of nutrients to the fetus, excretion of metabolites, and protection of the fetus from xenobiotics. METHODS: Human placental choriocarcinoma BeWo cells were used as a trophoblast model. PUFA-induced alteration in the gene expression of 84 transporters was investigated by a commercially available PCR array. Protein levels and the activity of transporters were assessed by western blotting and uptake experiments, respectively. The placental expression of the transporters was analyzed using pregnant Wistar rats. RESULTS: PUFAs (AA, EPA, and DHA) increased cystine/glutamate transporter xCT/SLC7A11, which mediates the cellular uptake of cystine coupled with the efflux of glutamate in human placental choriocarcinoma BeWo cells. These PUFAs also increased [14C]-cystine uptake in BeWo cells. PUFA-induced xCT/SLC7A11 mRNA expression was not blocked by nuclear factor-erythroid 2-related factor-2 (NRF2) knockdown. Reverse transcription (RT)-PCR analysis indicated that xCT/Slc7a11 mRNA was detected in rat placenta and the expression level at gestational day (GD) 12 was higher than that at GD 20. CONCLUSION: These results indicate that PUFAs promoted cystine uptake in placental cells by inducing xCT/SLC7A11 expression and NRF2 did not contribute to upregulation of xCT/SLC7A11 by PUFAs. Furthermore, xCT expression in rat placenta may change during pregnancy.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/76644
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 古堅 彩子

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