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Sodium orthovanadate inhibits p53-mediated apoptosis
https://repo.qst.go.jp/records/45712
https://repo.qst.go.jp/records/457126c84a3d4-3c86-4293-9411-a91edf0bc561
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-01-05 | |||||
| タイトル | ||||||
| タイトル | Sodium orthovanadate inhibits p53-mediated apoptosis | |||||
| 言語 | ||||||
| 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 | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Morita, Akinori
× Morita, Akinori× Yamamoto, Shinichi× Bing, Wang× Tanaka, Kaoru× Suzuki, Norio× Aoki, Shin× Ito, Azusa× Nanao, Tomohisa× Ohya, Souichirou× Zhu, Jin× Yoshino, Minako× Enomoto, Atsushi× Matsumoto, Yoshihisa× Funatsu, Osamu× Hosoi, Yoshio× Ikekita, Masahiko× 王 冰× 田中 薫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We recently reported a novel suppressive effect of sodium orthovanadate (vanadate) on the DNA-binding activity of p53. Here, we showed that vanadate had a more potent antiapoptotic activity than three other chemical p53 inhibitors, including pifithrin-alpha. Although the other agents inhibited p53's transcriptional activity, they did not suppress p53-dependent apoptosis in irradiated MOLT-4 cells. To investigate the cause for the different effects of vanadate and the other inhibitors, we chose PFT-alpha and PFT-mu (an inhibitor of the p53-mediated transcription-independent apoptotic pathway), as references, and determined their and vanadate's effect on p53-mediated apoptosis, with a focus on the transcription-independent pathway. We found that vanadate suppressed the p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and p53's interaction with Bcl-2. Vanadate also suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of the SaOS-2 cell line. Finally, we tested vanadate's potential as a radioprotector. Vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Our data demonstrate that vanadate can suppress both the transcription-dependent and the transcription-independent p53 pathways, and suggest that both pathways must be inhibited to completely block p53-mediated apoptosis. | |||||
| 書誌情報 |
Cancer Research 巻 70, 号 1, p. 257-265, 発行日 2010-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0008-5472 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1158/0008-5472.can-08-3771 | |||||
