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Cardioprotective effects of chloroquine pretreatment on ischemic and reperfusion injury via activation of ERK1/2 in isolated rat hearts
| Title: | Cardioprotective effects of chloroquine pretreatment on ischemic and reperfusion injury via activation of ERK1/2 in isolated rat hearts |
| Authors: | Murase, Ryota Browse this author | | Shingu, Yasushige Browse this author →KAKEN DB | | Wakasa, Satoru Browse this author →KAKEN DB |
| Keywords: | Chloroquine | | Extracellular signal-regulated kinase | | Ischemic and reperfusion injury | | Cardioprotection |
| Issue Date: | 1-Oct-2022 |
| Publisher: | Springer |
| Journal Title: | Molecular Biology Reports |
| Volume: | 49 |
| Issue: | 10 |
| Start Page: | 9429 |
| End Page: | 9436 |
| Publisher DOI: | 10.1007/s11033-022-07801-7 |
| Abstract: | Purpose Several therapeutic agents have been found to prevent myocardial ischemic and reperfusion (I/R) injury after cardiac surgery; however, no drug is routinely used to afford cardioprotective benefits in clinical settings. Herein, we aimed to determine whether chloroquine (CQ) pretreatment attenuates I/R injury after global ischemia in isolated rat hearts and elucidate mechanisms underlying the effects of CQ. Methods Isolated rat hearts were subjected to 30-min global ischemia, followed by 60-min reperfusion with Krebs-Henseleit buffer (KHB). Immediately before ischemia, 10 mL of pretreatment solutions (KHB, n = 4 or KHB + CQ [100 mu M], n = 4) were injected through the aortic root. Cardiac function was examined based on the rate pressure product (RPP). Myocardial apoptosis was evaluated using TUNEL staining. To assess the reperfusion ischemia salvage kinase pathway, protein expression levels of AKT and extracellular signal-regulated kinase (ERK1/2) were determined using western blotting. To investigate the role of ERK1/2, an ERK1/2 selective inhibitor was used in eight additional rats. Results The recovery rate of the RPP was higher in the KHB + CQ group than in the KHB group 60 min after I/R (KHB, 44 +/- 3% vs. KHB + CQ, 69 +/- 7%; P = 0.019, d = 2.2). CQ pretreatment reduced apoptosis and enhanced the phosphorylation of ERK1/2; however, AKT phosphorylation was unaltered. In addition, the ERK1/2 inhibitor abolished CQ-mediated cardioprotective effects. Conclusions CQ pretreatment showed protective effects on cardiac function after I/R by activating ERK1/2. |
| Rights: | This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11033-022-07801-7 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/90589 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 新宮 康栄
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