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S1P 3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species
http://hdl.handle.net/2297/21766
http://hdl.handle.net/2297/21766d9a81b41-ff56-4feb-a29f-84f6cc50b09a
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ME-PR-TAKUWA-Y-484.pdf (8.0 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-10-03 | |||||
| タイトル | ||||||
| タイトル | S1P 3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species | |||||
| 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 | |||||
| 著者 |
Takuwa, Noriko
× Takuwa, Noriko× Ohkura, Sei-Ichiro× Takashima, Shin-ichiro× Ohtani, Keisuke× Okamoto, Yasuo× Tanaka, Tamotsu× Hirano, Kaoru× Usui, Soichiro× Wang, Fei× Du, Wa× Yoshioka, Kazuaki× Banno, Yoshiko× Sasaki, Motoko× Ichi, Ikuyo× Okamura, Miwa× Sugimoto, Naotoshi× Mizugishi, Kiyomi× Nakanuma, Yasuni× Ishii, Isao× Takamura, Masayuki× Kaneko, Shuichi× Kojo, Shosuke× Satouchi, Kiyoshi× Mitumori, Kunitoshi× Chun, Jerold× Takuwa, Yoh |
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| 提供者所属 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 金沢大学医薬保健研究域医学系 | |||||
| 書誌情報 |
Cardiovascular Research 巻 85, 号 3, p. 484-493, 発行日 2010-02-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0008-6363 | |||||
| NCID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA0059904X | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1093/cvr/cvp312 | |||||
| 出版者 | ||||||
| 出版者 | Oxford University Press (OUP) | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Aims Sphingosine kinase 1 (SPHK1), its product sphingosine-1-phosphate (S1P), and S1P receptor subtypes have been suggested to play protective roles for cardiomyocytes in animal models of ischaemic preconditioning and cardiac ischaemia/reperfusion injury. To get more insight into roles for SPHK1 in vivo, we have generated SPHK1-transgenic (TG) mice and analysed the cardiac phenotype.Methods and results SPHK1-TG mice overexpressed SPHK1 in diverse tissues, with a nearly 20-fold increase in enzymatic activity. The TG mice grew normally with normal blood chemistry, cell counts, heart rate, and blood pressure. Unexpectedly, TG mice with high but not low expression levels of SPHK1 developed progressive myocardial degeneration and fibrosis, with upregulation of embryonic genes, elevated RhoA and Rac1 activity, stimulation of Smad3 phosphorylation, and increased levels of oxidative stress markers. Treatment of juvenile TG mice with pitavastatin, an established inhibitor of the Rho family G proteins, or deletion of S1P3, a major myocardial S1P receptor subtype that couples to Rho GTPases and transactivates Smad signalling, both inhibited cardiac fibrosis with concomitant inhibition of SPHK1-dependent Smad-3 phosphorylation. In addition, the anti-oxidant N-2-mercaptopropyonylglycine, which reduces reactive oxygen species (ROS), also inhibited cardiac fibrosis. In in vivo ischaemia/reperfusion injury, the size of myocardial infarct was 30 decreased in SPHK1-TG mice compared with wild-type mice.Conclusion These results suggest that chronic activation of SPHK1-S1P signalling results in both pathological cardiac remodelling through ROS mediated by S1P3 and favourable cardioprotective effects. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
