PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs
Myocardial ischemia/reperfusion (I/R) injury is a major complication of reperfusion therapy in myocardial infarction. Ischemic myocardium produces a variety of peptides. We recently identified PDRPS7 as a novel peptide in cardiomyocytes that can be induced by hypoxia. However, the role of PDRPS7 is...
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Online Access: | https://doi.org/10.1002/2211-5463.12822 |
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doaj-9925d1ee06044a77a505b83233cf29b22021-07-03T12:45:36ZengWileyFEBS Open Bio2211-54632020-04-0110459360610.1002/2211-5463.12822PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKsYulian Duan0Siyuan Cheng1Liang Jia2Zhao Zhang3Leilei Chen4College of Life Sciences Nanjing Normal University ChinaDepartment of Cardiology the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University ChinaDepartment of Cardiology the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University ChinaCollege of Life Sciences Nanjing Normal University ChinaDepartment of Cardiology the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University ChinaMyocardial ischemia/reperfusion (I/R) injury is a major complication of reperfusion therapy in myocardial infarction. Ischemic myocardium produces a variety of peptides. We recently identified PDRPS7 as a novel peptide in cardiomyocytes that can be induced by hypoxia. However, the role of PDRPS7 is unknown. Here, we investigated the effects of PDRPS7 on hypoxia/reoxygenation (H/R)‐induced injury in rat cardiomyoblast H9c2 cells and NRCMs. We found that PDRPS7 improved cell survival and attenuated lactate dehydrogenase leakage following H/R in H9c2 cells and NRCMs. PDRPS7 also alleviated H/R‐induced pulsation reduction in NRCMs. Moreover, H/R‐induced cell apoptosis was decreased in the presence of PDRPS7. H/R‐induced reactive oxygen species generation was reduced by PDRPS7; in addition, PDRPS7 did not impact H2O2‐induced cell injury. Signaling analysis demonstrated that H/R increased the phosphorylation levels of JNKs, ERKs, and p38 mitogen‐activated protein kinases. However, PDRPS7 only attenuated H/R‐induced JNK phosphorylation, but not phosphorylation of ERKs and p38. PDRPS7 protected cardiomyocytes from apoptosis by inhibiting JNK phosphorylation and c‐Jun phosphorylation pathways, markedly upregulating anti‐apoptotic Bcl‐2 expression and inhibiting that of pro‐apoptotic Bax and cleaved caspase‐3. Importantly, pharmacological activation of JNKs diminished the protective effect of PDRPS7 in terms of cell survival against H/R stimulation. In summary, our study identified PDRPS7 as a novel cardioprotective peptide against H/R challenge and this action was mediated, at least in part, through inactivation of JNKs.https://doi.org/10.1002/2211-5463.12822cardiomyocyteshypoxia/reoxygenationJNKsPDRPS7peptides |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yulian Duan Siyuan Cheng Liang Jia Zhao Zhang Leilei Chen |
spellingShingle |
Yulian Duan Siyuan Cheng Liang Jia Zhao Zhang Leilei Chen PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs FEBS Open Bio cardiomyocytes hypoxia/reoxygenation JNKs PDRPS7 peptides |
author_facet |
Yulian Duan Siyuan Cheng Liang Jia Zhao Zhang Leilei Chen |
author_sort |
Yulian Duan |
title |
PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs |
title_short |
PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs |
title_full |
PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs |
title_fullStr |
PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs |
title_full_unstemmed |
PDRPS7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of JNKs |
title_sort |
pdrps7 protects cardiac cells from hypoxia/reoxygenation injury through inactivation of jnks |
publisher |
Wiley |
series |
FEBS Open Bio |
issn |
2211-5463 |
publishDate |
2020-04-01 |
description |
Myocardial ischemia/reperfusion (I/R) injury is a major complication of reperfusion therapy in myocardial infarction. Ischemic myocardium produces a variety of peptides. We recently identified PDRPS7 as a novel peptide in cardiomyocytes that can be induced by hypoxia. However, the role of PDRPS7 is unknown. Here, we investigated the effects of PDRPS7 on hypoxia/reoxygenation (H/R)‐induced injury in rat cardiomyoblast H9c2 cells and NRCMs. We found that PDRPS7 improved cell survival and attenuated lactate dehydrogenase leakage following H/R in H9c2 cells and NRCMs. PDRPS7 also alleviated H/R‐induced pulsation reduction in NRCMs. Moreover, H/R‐induced cell apoptosis was decreased in the presence of PDRPS7. H/R‐induced reactive oxygen species generation was reduced by PDRPS7; in addition, PDRPS7 did not impact H2O2‐induced cell injury. Signaling analysis demonstrated that H/R increased the phosphorylation levels of JNKs, ERKs, and p38 mitogen‐activated protein kinases. However, PDRPS7 only attenuated H/R‐induced JNK phosphorylation, but not phosphorylation of ERKs and p38. PDRPS7 protected cardiomyocytes from apoptosis by inhibiting JNK phosphorylation and c‐Jun phosphorylation pathways, markedly upregulating anti‐apoptotic Bcl‐2 expression and inhibiting that of pro‐apoptotic Bax and cleaved caspase‐3. Importantly, pharmacological activation of JNKs diminished the protective effect of PDRPS7 in terms of cell survival against H/R stimulation. In summary, our study identified PDRPS7 as a novel cardioprotective peptide against H/R challenge and this action was mediated, at least in part, through inactivation of JNKs. |
topic |
cardiomyocytes hypoxia/reoxygenation JNKs PDRPS7 peptides |
url |
https://doi.org/10.1002/2211-5463.12822 |
work_keys_str_mv |
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