ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways
Increasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.873614/full |
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| author | Xuejun Wang Xuejun Wang Li Zhang Mengwen Feng Zhongqing Xu Zijie Cheng Zijie Cheng Lingmei Qian Lingmei Qian |
| author_facet | Xuejun Wang Xuejun Wang Li Zhang Mengwen Feng Zhongqing Xu Zijie Cheng Zijie Cheng Lingmei Qian Lingmei Qian |
| author_sort | Xuejun Wang |
| collection | DOAJ |
| description | Increasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11-residue furn-cleaved fragment (ELA-11) is still unclear. We first administrated ELA-11 in DOX-injured mice and measured the cardiac function and investigated the effect of ELA-11 in vivo. We found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. In vitro, ELA-11 regulated the sensitivity towards apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway. Similarly, ELA-11 inhibited oxidative stress-induced apoptosis in cobalt chloride (CoCl2)-injured cardiomyocytes. Moreover, ELA-11 protected cardiomyocyte by interacting with Apelin receptor (APJ) by using 4-oxo-6-((pyrimidin-2-ylthio) methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221). Hence, our results indicated a protective role of ELA-11 in oxidative stress-induced apoptosis in DOX-induced myocardial injury. |
| first_indexed | 2024-04-11T21:19:59Z |
| format | Article |
| id | doaj.art-fce2bce907b54094b228804f7057016a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T21:19:59Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-fce2bce907b54094b228804f7057016a2022-12-22T04:02:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.873614873614ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathwaysXuejun Wang0Xuejun Wang1Li Zhang2Mengwen Feng3Zhongqing Xu4Zijie Cheng5Zijie Cheng6Lingmei Qian7Lingmei Qian8Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaIncreasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11-residue furn-cleaved fragment (ELA-11) is still unclear. We first administrated ELA-11 in DOX-injured mice and measured the cardiac function and investigated the effect of ELA-11 in vivo. We found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. In vitro, ELA-11 regulated the sensitivity towards apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway. Similarly, ELA-11 inhibited oxidative stress-induced apoptosis in cobalt chloride (CoCl2)-injured cardiomyocytes. Moreover, ELA-11 protected cardiomyocyte by interacting with Apelin receptor (APJ) by using 4-oxo-6-((pyrimidin-2-ylthio) methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221). Hence, our results indicated a protective role of ELA-11 in oxidative stress-induced apoptosis in DOX-induced myocardial injury.https://www.frontiersin.org/articles/10.3389/fphar.2022.873614/fullELA-11doxorubicinheart failureapoptosisoxidative stress |
| spellingShingle | Xuejun Wang Xuejun Wang Li Zhang Mengwen Feng Zhongqing Xu Zijie Cheng Zijie Cheng Lingmei Qian Lingmei Qian ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways Frontiers in Pharmacology ELA-11 doxorubicin heart failure apoptosis oxidative stress |
| title | ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways |
| title_full | ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways |
| title_fullStr | ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways |
| title_full_unstemmed | ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways |
| title_short | ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways |
| title_sort | ela 11 protects the heart against oxidative stress injury induced apoptosis through erk mapk and pi3k akt signaling pathways |
| topic | ELA-11 doxorubicin heart failure apoptosis oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.873614/full |
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