Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4

村越, 道生; Murakoshi, Michio; Koike, Yuhi; Koyama, Shin; Usami, Shinichi; Kamiya, Kazusaku; Ikeda, Katsuhisa; Haga, Yoichi; Tsumoto, Kohei; Nakamura, Hiroyuki; Hirasawa, Noriyasu; Ishihara, Kenji; Wada, Hiroshi

doi:10.1016/j.anl.2022.03.009

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Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4

https://doi.org/10.24517/00065624

名前 / ファイル	ライセンス	アクション
TE-PR-MURAKOSHI-M-2022-937.pdf (626.3 kB)

Item type

学術雑誌論文 / Journal Article(1)

公開日

2022-07-14

タイトル

Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4

言語

eng

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_6501

資源タイプ

journal article

ID登録

10.24517/00065624

ID登録タイプ

JaLC

著者

Murakoshi, Michio

WEKO 86506
e-Rad 70570901

	Murakoshi, Michio

Search repository

Koike, Yuhi
Koyama, Shin
Usami, Shinichi

Kamiya, Kazusaku

Ikeda, Katsuhisa

Haga, Yoichi
Tsumoto, Kohei

Nakamura, Hiroyuki

Hirasawa, Noriyasu

Ishihara, Kenji

Wada, Hiroshi

著者別表示

村越, 道生

提供者所属

内容記述タイプ

Other

内容記述

金沢大学理工研究域フロンティア工学系

書誌情報

Auris Nasus Larynx

巻 49, 号 6, p. 928-937, 発行日 2022-12-01

ISSN

収録物識別子タイプ

ISSN

収録物識別子

0385-8146

NCID

収録物識別子タイプ

NCID

収録物識別子

AA00061157

DOI

関連識別子

10.1016/j.anl.2022.03.009

出版者

Oto-Rhino-Laryngological Society of Japan 日本耳鼻咽喉科頭頸部外科学会 / Elsevier

抄録

内容記述タイプ

Abstract

内容記述

Objective
Pendrin is a transmembrane protein encoded by the SLC26A4 gene that functions in maintaining ion concentrations in the endolymph of the inner ear, most likely by acting as a chloride/bicarbonate transporter. Variants in the SLC26A4 gene are responsible for sensorineural hearing loss. Although pendrin localizes to the plasma membrane, we previously identified that 8 missense allele products of SLC26A4 were retained in the intracellular region and lost their anion exchange function. We also found that 10 mM salicylate induced the translocation of 4 out of 8 allele products from the intracellular region to the plasma membrane and restored their anion exchanger activity. However, since 10 mM salicylate exhibits cytotoxicity, the use of chemical compounds with less cell toxicity is needed. In the present study, therefore, salicylate derivatives were used as the chemical compounds and their effects on the p.H723R allele products of SLC26A4 were investigated.
Methods
HEK293 cells were transfected with the cDNA of p.H723R. Cell proliferation, viability and toxicity assays were performed to investigate the response and health of cells in culture after treatment with four types of salicylate derivatives, i.e., 2-hydroxybenzyl alcohol, 2,3-dihydroxybenzoic acid, 2’-hydroxyacetophenone and methyl salicylate. The effects of these salicylate derivatives on the localization of the p.H723R were investigated by immunofluorescence microscopy.
Results
The application of 10 mM salicylate showed an increase in cell toxicity and decrease in cell viability, leading to a significant decrease in cell proliferation. In contrast, the application of 1 mM salicylate derivatives did not show any significant increase in cell toxicity and decrease in cell viability, corresponding to a logarithmic increase in cell concentration with an increase in culture time. Immunofluorescence experiments showed that the p.H723R retained in the endoplasmic reticulum (ER). Among the salicylate derivatives applied, 2-hydroxybenzyl alcohol induced the translocation of p.H723R from the ER to the plasma membrane 3 h after its application.
Conclusion
The results obtained showed that 2-hydroxybenzyl alcohol restored the localization of the p.H723R allele products of SLC26A4 from the ER to the plasma membrane at a concentration of 1 mM by 3 h after its administration with less cytotoxicity than 10 mM salicylate.

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Embargo Period 12 months

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出版タイプResource

http://purl.org/coar/version/c_ab4af688f83e57aa

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http://www.jibika.or.jp/

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2023-07-27 12:39:26.412638

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Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4

× Murakoshi, Michio

× Koike, Yuhi

× Koyama, Shin

× Usami, Shinichi

× Kamiya, Kazusaku

× Ikeda, Katsuhisa

× Haga, Yoichi

× Tsumoto, Kohei

× Nakamura, Hiroyuki

× Hirasawa, Noriyasu

× Ishihara, Kenji

× Wada, Hiroshi

× 村越, 道生

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