Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells

• Material Type: 博士論文
• Title: Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells
• Author/Editor: Tada, Tomoki; Aki, Kensaku; Oboshi, Wataru; Kawazoe, Kazuyoshi; Yasui, Toshiyuki; Hosoi, Eiji
• Author Heading: Tada, Tomoki; Aki, Kensaku; Oboshi, Wataru; Kawazoe, Kazuyoshi; Yasui, Toshiyuki; Hosoi, Eiji
• Publication, Distribution, etc.: Dove Press
• Publication Date: 2016-09-26
• Publication Date (W3CDTF): 2016-09-26
• Alternative Title: ホルボール12-ミリスタート 13-アセタート分化誘導による巨核球系細胞を用いた血小板機能に対する各種薬剤効果の評価; Effects of various drugs on platelet functions
• Periodical title: Drug Design, Development and Therapy
• No. or year of volume/issue: 10
• Volume: 10
• Pages: 3099-3107
• ISSN (Periodical Title): ISSN : 1177-8881
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-23
• Dissertation Number: 甲第3037号
• Degree Type: 博士（保健学）
• Text Language Code: eng
• Subject Heading: platelets; intracellular Ca2+ concentration ([Ca2+]i); aspirin; cilostazol; ibuprofen; sodium valproate
• Target Audience: 一般
• Note (General): Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Materials and methods: Human erythroid leukemia (HEL) cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i) mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM) and cilostazol (5–10 µM) significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM) and sodium valproate (50–1,000 µg/mL) also significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. Furthermore, the interaction effects of the simultaneous combined use of aspirin and ibuprofen or sodium valproate were evaluated. When the inhibitory effect of aspirin was higher than that of ibuprofen, the effect of aspirin was reduced, whereas when the inhibitory effect of aspirin was lower than that of ibuprofen, the effect of ibuprofen was reduced. The combination of aspirin and sodium valproate synergistically inhibited thrombin-induced [Ca2+]i. Conclusion: It is possible to induce HEL cells to differentiate into megakaryocytes, which are a useful model for the study of platelet functions, and the quantification of the inhibition of thrombin-induced increases in [Ca2+]i is applicable to the evaluation of the effects of various drugs on platelets.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): Copyrihgt© 2016 Tada et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php)
• Related Material (DOI): 10.2147/DDDT.S115910
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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