PMID- 30712664 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20200316 IS - 1532-3102 (Electronic) IS - 0143-4004 (Linking) VI - 75 DP - 2019 Jan TI - Analysis of the effects of polyunsaturated fatty acids on transporter expressions using a PCR array: Induction of xCT/SLC7A11 in human placental BeWo cells. PG - 34-41 LID - S0143-4004(18)30665-9 [pii] LID - 10.1016/j.placenta.2018.11.010 [doi] AB - 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 [(14)C]-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. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Ono, Kanako AU - Ono K AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan. FAU - Furugen, Ayako AU - Furugen A AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan. FAU - Kurosawa, Yuko AU - Kurosawa Y AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan. FAU - Jinno, Naoko AU - Jinno N AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan. FAU - Narumi, Katsuya AU - Narumi K AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan. FAU - Kobayashi, Masaki AU - Kobayashi M AD - Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan. FAU - Iseki, Ken AU - Iseki K AD - Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan; Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan. Electronic address: ken-i@pharm.hokudai.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181127 PL - Netherlands TA - Placenta JT - Placenta JID - 8006349 RN - 0 (Amino Acid Transport System y+) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (NF-E2-Related Factor 2) RN - 0 (SLC7A11 protein, human) SB - IM MH - Amino Acid Transport System y+/*metabolism MH - Animals MH - Cell Line MH - Fatty Acids, Unsaturated/*physiology MH - Female MH - Humans MH - NF-E2-Related Factor 2/metabolism MH - Placenta/*metabolism MH - Pregnancy MH - Rats, Wistar OTO - NOTNLM OT - Arachidonic acid (AA) OT - Docosahexaenoic acid (DHA) OT - Eicosapentaenoic acid (EPA) OT - Placenta OT - Transporter OT - xCT/SLC7A11 EDAT- 2019/02/05 06:00 MHDA- 2020/03/17 06:00 CRDT- 2019/02/05 06:00 PHST- 2018/07/18 00:00 [received] PHST- 2018/11/04 00:00 [revised] PHST- 2018/11/26 00:00 [accepted] PHST- 2019/02/05 06:00 [entrez] PHST- 2019/02/05 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] AID - S0143-4004(18)30665-9 [pii] AID - 10.1016/j.placenta.2018.11.010 [doi] PST - ppublish SO - Placenta. 2019 Jan;75:34-41. doi: 10.1016/j.placenta.2018.11.010. Epub 2018 Nov 27.