Kagoshima University · Division of Fisheries Sciences, School of Agriculture, Fisheries and Veterinary Medicine · 准教授

Research keywordsヒ素・エピジェネティクス・酸化ストレス・遺伝子変異・食品・脂質代謝・亜鉛・マイクロシスチン-LR・OATP1B3

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• Takumi S., Tomioka M., Yunoki Y., Eto R., Komatsu Y., Shiozaki K., Komatsu M. . Microcystin-LR-induced epithelial-mesenchymal transition-like cells acquire resistance to multi-toxins .2023 · 担当区分： 筆頭著者 記述言語： 英語 掲載種別： 研究論文（学術雑誌） 出版者・発行元： Toxicon The protein phosphatase inhibitor microcystin-LR (MC-LR), a hepatocyte-selective cyanotoxin, induces phenotypic changes in HEK293 OATP1B3-expressing (HEK293-OATP1B3) cells, which include cytoskeletal reorganization (HEK293-OATP1B3-AD) and anoikis resistance (HEK293-OATP1B3-FL) transformed cells, respectively. These cells acquire resistance to MC-LR and partial epithelial-mesenchymal transition (EMT) characteristics. In cancer cells, EMT is generally involved in multi-drug resistance. Here, we focused on the multi-drug resistance of HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. The MTT assay and immunoblotting were conducted to examine the responses of HEK293-OATP1B3, HEK293-OATP1B3-AD, and HEK293-OATP1B3-FL cells to multiple toxins and drugs that function as substrates for OATP1B3, including MC-LR, nodularin (Nod), okadaic acid (OA), and cisplatin (CDDP). HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells were more resistant to MC-LR, Nod, and OA than HEK293-OATP1B3 cells. Conversely, the three cell types were equivalently sensitive to CDDP. By using protein phosphatase assay, the reduction of the inhibitory effect of MC-LR and Nod on phosphatase activity might be one reason for the resistance to MC-LR and Nod in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. Furthermore, the parental HEK293-OATP1B3 cells showed enhanced p53 phosphorylation and stabilization after MC-LR exposure, while p53 phosphorylation was attenuated in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. Moreover, in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells, AKT phosphorylation was higher than that of the parental HEK293-OATP1B3 cell line. These results suggest that the multi-toxin resistance observed in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells is associated with AKT activation and p53 inactivation. DOI： 10.1016/j.toxicon.2023.107592 Scopus PubMed
• 食品の科学2022 · 南江堂 2022年3月 （ ISBN: 9784524228720 ）
• 健康・栄養科学シリーズ 食べ物と健康 食品の科学 改訂第３版2022 · 南江堂 2022年3月
• Eel Serum Synergistically Enhances Growth of Fish Cell Line GAKS2021 · Memoirs of Faculty of Fisheries Kagoshima University 2021年

• 動脈硬化症の予防に有効な鹿児島県産の食材の探索2025 · 資金種別： 競争的資金 配分額： 400000円
• ウナギ緑色蛍光タンパク質UnaGの生理機能に関する研究2024 · 担当区分： 研究代表者 資金種別： 競争的資金 配分額： 900000円
• ヒ素代謝物が脂質代謝経路へ及ぼす影響2020 · 資金種別： 競争的資金
• 食品成分による動脈硬化症予防法の開発2016 · 2016年4月 - 2020年3月

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