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https://ir.cnu.edu.tw/handle/310902800/29634
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| 標題: | KMUP-1 Attenuates Endothelin-1-Induced Cardiomyocyte Hypertrophy through Activation of Heme Oxygenase-1 and Suppression of the Akt/GSK-3 beta, Calcineurin/NFATc4 and RhoA/ROCK Pathways |
| 作者: | Liou, Shu-Fen
Hsu, Jong-Hau
Chen, You-Ting
Chen, Ing-Jun
Yeh, Jwu-Lai |
| 貢獻者: | 藥學系 |
| 關鍵字: | KMUP-1
endothelin-1
cardiac hypertrophy
reactive oxygen species
heme oxygenase-1 |
| 日期: | 2015-06 |
| 上傳時間: | 2016-04-19 19:02:46 (UTC+8) |
| 出版者: | Mdpi Ag |
| 摘要: | The signaling cascades of the mitogen activated protein kinase (MAPK) family, calcineurin/NFATc4, and PI3K/Akt/GSK3, are believed to participate in endothelin-1 (ET-1)-induced cardiac hypertrophy. The aim of this study was to investigate whether KMUP-1, a synthetic xanthine-based derivative, prevents cardiomyocyte hypertrophy induced by ET-1 and to elucidate the underlying mechanisms. We found that in H9c2 cardiomyocytes, stimulation with ET-1 (100 nM) for 4 days induced cell hypertrophy and enhanced expressions of hypertrophic markers, including atrial natriuretic peptide and brain natriuretic peptide, which were all inhibited by KMUP-1 in a dose-dependent manner. In addition, KMUP-1 prevented ET-1-induced intracellular reactive oxygen species generation determined by the DCFH-DA assay in cardiomyocytes. KMUP-1 also attenuated phosphorylation of ERK1/2 and Akt/GSK-3, and activation of calcineurin/NFATc4 and RhoA/ROCK pathways induced by ET-1. Furthermore, we found that the expression of heme oxygenase-1 (HO-1), a stress-response enzyme implicated in cardio-protection, was up-regulated by KMUP-1. Finally, KMUP-1 attenuated ET-1-stimulated activator protein-1 DNA binding activity. In conclusion, KMUP-1 attenuates cardiomyocyte hypertrophy induced by ET-1 through inhibiting ERK1/2, calcineurin/NFATc4 and RhoA/ROCK pathways, with associated cardioprotective effects via HO-1 activation. Therefore, KMUP-1 may have a role in pharmacological therapy of cardiac hypertrophy. |
| 關聯: | Molecules, v.20 n.6, pp.10435-10449 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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