WEKO3
アイテム
Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters
https://tokushima-u.repo.nii.ac.jp/records/2010585
https://tokushima-u.repo.nii.ac.jp/records/20105858c6b979a-0314-43ad-a34a-7c82b71db1b6
| 名前 / ファイル | ライセンス | アクション |
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febs_290_4_1027.pdf (1.59 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||||||||||
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| 公開日 | 2022-11-30 | |||||||||||||||||||||||||||||||
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| アクセス権 | open access | |||||||||||||||||||||||||||||||
| 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 | |||||||||||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1111/febs.16623 | |||||||||||||||||||||||||||||||
| 関連名称 | 10.1111/febs.16623 | |||||||||||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||||||||||
| 出版タイプ | AM | |||||||||||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||||||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||||||||||
| タイトル | Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters | |||||||||||||||||||||||||||||||
| タイトル別表記 | ||||||||||||||||||||||||||||||||
| その他のタイトル | Mechanism of apoptosis induction by tocopheryl esters | |||||||||||||||||||||||||||||||
| 著者 |
Ray, Manobendro Nath
× Ray, Manobendro Nath
× 大園, 瑞音
WEKO
1435
× 中尾, 允泰
WEKO
379
× 佐野, 茂樹
WEKO
1146
× 小暮, 健太朗
WEKO
1139
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| 内容記述 | α-Tocopheryl succinate (TS), a redox-silent succinyl ester of natural α-Tocopherol, has emerged as a novel anticancer agent. However, the underlying mechanism is unclear. We found that the terminal dicarboxylic moiety of tocopheryl esters contributes to apoptosis induction and thus cytotoxicity. To further examine this relationship, we compared the pro-apoptotic activity of TS, which has four carbon atoms in the terminal dicarboxylic moiety, to that of a newly synthesized, tocopheryl glutarate (Tglu), which has five. Cytotoxicity assays in vitro confirmed that TS stimulated apoptosis, while Tglu was non-cytotoxic. In investigating biological mechanisms leading to these opposing effects, we found that TS caused an elevation of intracellular superoxide, but Tglu did not. TS increased intracellular Ca2+ in cultured cells, suggesting induction of endoplasmic reticulum (ER) stress; however, Tglu did not affect Ca2+ homeostasis. 1,4,5-trisphosphate (IP3) receptor antagonist 2-Aminoethyl diphenylborinate (2-APB) decreased TS-induced intracellular Ca2+, restored mitochondrial activity and cell viability in TS-treated cells, establishing the ER-mitochondria relationship in apoptosis induction. Moreover, real-time PCR, immunostaining and Western blotting assays revealed that TS downregulated glucose-regulated protein 78 (GRP78), which maintains ER homeostasis and promotes cell survival. Conversely, Tglu upregulates GRP78. Taken together, our results suggest a model in which TS-mediated superoxide production and GRP78 inhibition induce ER stress, which elevates intracellular Ca2+ and depolarizes mitochondria, leading to apoptosis. Because Tglu does not affect superoxide generation and increases GRP78 expression, it inhibits ER stress and is thereby non-cytotoxic. Our research provides insight into the structure-activity relationship of tocopheryl esters regarding the induction of apoptosis. | |||||||||||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||||||||||
| 主題 | α-Tocopheryl ester | |||||||||||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||||||||||
| 主題 | Structure-activity relationship | |||||||||||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||||||||||
| 主題 | Endoplasmic reticulum stress | |||||||||||||||||||||||||||||||
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| 主題 | GRP78 | |||||||||||||||||||||||||||||||
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| 主題 | Apoptosis | |||||||||||||||||||||||||||||||
| 書誌情報 |
en : The FEBS Journal 巻 290, 号 4, p. 1027-1048, 発行日 2022-09-09 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||||||||||
| 収録物識別子 | 17424658 | |||||||||||||||||||||||||||||||
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||||||||||
| 収録物識別子 | 1742464X | |||||||||||||||||||||||||||||||
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| 収録物識別子タイプ | NCID | |||||||||||||||||||||||||||||||
| 収録物識別子 | AA11998513 | |||||||||||||||||||||||||||||||
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| 収録物識別子タイプ | NCID | |||||||||||||||||||||||||||||||
| 収録物識別子 | AA12092067 | |||||||||||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||||||||||
| 出版者 | Federation of European Biochemical Societies | |||||||||||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||||||||||
| 出版者 | Wiley | |||||||||||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||||||||||
| 権利情報 | This is the peer reviewed version of the following article: Ray, M.N., Ozono, M., Nakao, M., Sano, S. and Kogure, K. (2023), Only one carbon difference determines the pro-apoptotic activity of α-tocopheryl esters. FEBS J, 290: 1027-1048., which has been published in final form at https://doi.org/10.1111/febs.16623. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. | |||||||||||||||||||||||||||||||
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| 識別子 | 393054 | |||||||||||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||||||||||
