Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells

Miyazawa, Yuki; Furugen, Ayako; Aoyagi, Ryoichi; Kosugi, Haruna; Nishimura, Ayako; Umazume, Takeshi; Narumi, Katsuya; Kobayashi, Masaki

Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells

Miyazawa, Yuki; Furugen, Ayako; Aoyagi, Ryoichi et al.

Toxicology in vitro, 2024, 101, 105934

Permalink : https://hdl.handle.net/2115/97270

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アクセス権	open access
URI	https://hdl.handle.net/2115/97270
タイトル	Alteration in folate carrier expression via histone deacetylase inhibition in BeWo human placental choriocarcinoma cells
著者	Miyazawa, Yuki ; Furugen, Ayako ; Aoyagi, Ryoichi ; Kosugi, Haruna ; Nishimura, Ayako ; Umazume, Takeshi ; Narumi, Katsuya ; Kobayashi, Masaki
著者名 Miyazawa, Yuki
e-Rad_Researcher 90767261 著者名 Furugen, Ayako
著者名 Aoyagi, Ryoichi
著者名 Kosugi, Haruna
著者名 Nishimura, Ayako
e-Rad_Researcher 00807935 著者名 Umazume, Takeshi
e-Rad_Researcher 90746752 著者名 Narumi, Katsuya
e-Rad_Researcher 70431319 著者名 Kobayashi, Masaki
言語	英語
キーワード	FRα/FOLR1
	HDAC
	PCFT/SLC46A1
	Placenta
	RFC/SLC19A1
	Valproic acid
発行日	2024-12
出版者	Elsevier
収録物名	Toxicology in vitro
巻(号)	101
ページ	105934
抄録	Folates are essential nutrients for fetal development during pregnancy. Valproic acid (VPA), an inhibitor of histone deacetylases (HDACs), alters the expression of folate carriers in placental cells; however, the underlying mechanisms remain unclear. Here, we aimed to determine the profiles of folate carriers (folate receptor alpha [FOLR1], solute carrier [SLC]-19A1, and SLC46A1) after inhibition of HDACs, especially class I and IIa HDACs, using different inhibitors and gene knockdown tests. Quantitative polymerase chain reaction revealed that BeWo cells (a trophoblast model) expressed HDACs and folate carriers, similar to human placental villi. FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. VPA and apicidin upregulated the expression of SLC46A1. These inhibitors downregulated SLC19A1 expression. TMP269 (a class IIa inhibitor) did not affect folate carrier levels. HDAC1/2 knockdown upregulated FOLR1 and SLC46A1 levels, whereas HDAC1/3 knockdown downregulated FOLR1 levels. Our findings suggest that the pharmacological inhibition of class I HDACs alters the expression of folate carriers in BeWo cells. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0887-2333
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.tiv.2024.105934