Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells
Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA da...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00223/full |
| _version_ | 1818864065506705408 |
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| author | Dandan Zhou Jinqiang Zhuang Yihui Wang Dandan Zhao Lidong Zhao Shun Zhu Shun Zhu Jinjun Pu Ming Yin Hongyu Zhang Zejian Wang Jiang Hong |
| author_facet | Dandan Zhou Jinqiang Zhuang Yihui Wang Dandan Zhao Lidong Zhao Shun Zhu Shun Zhu Jinjun Pu Ming Yin Hongyu Zhang Zejian Wang Jiang Hong |
| author_sort | Dandan Zhou |
| collection | DOAJ |
| description | Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA damage in cardiomyocytes. In our study, we established an oxygen glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells and found that propofol decreased reactive oxygen species (ROS) levels and suppressed cell apoptosis induced by OGD/R in H9c2 cells. In addition, propofol significantly reduced the molecular marker of DNA damage and inhibited double-strand breaks of DNA damage induced by OGD/R in H9c2 cells in a dose-dependent manner. Furthermore, we investigated the molecular mechanisms and demonstrated that propofol inhibited forkhead box O 1 (FoxO1) phosphorylation and increased FoxO1 nuclear translocation through inhibition of protein kinase B (Akt) and adenosine 5’-monophosphate-activated protein kinase (AMPK) pathways. The protective effects of propofol against oxidative stress-induced DNA damage were reversed by silencing FoxO1. Taken together, our results suggest that oxidative stress aggravates DNA damage and apoptosis in H9C2 cells, which can be reversed by propofol via FoxO1 nuclear translocation. |
| first_indexed | 2024-12-19T10:25:44Z |
| format | Article |
| id | doaj.art-81f96dc074d04822833fcfb77e9d0b19 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T10:25:44Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-81f96dc074d04822833fcfb77e9d0b192022-12-21T20:25:55ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-03-011010.3389/fphys.2019.00223434441Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 CellsDandan Zhou0Jinqiang Zhuang1Yihui Wang2Dandan Zhao3Lidong Zhao4Shun Zhu5Shun Zhu6Jinjun Pu7Ming Yin8Hongyu Zhang9Zejian Wang10Jiang Hong11Department of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Emergency Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Biomedicine, KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, NorwaySchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Internal and Emergency Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, ChinaIschemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA damage in cardiomyocytes. In our study, we established an oxygen glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells and found that propofol decreased reactive oxygen species (ROS) levels and suppressed cell apoptosis induced by OGD/R in H9c2 cells. In addition, propofol significantly reduced the molecular marker of DNA damage and inhibited double-strand breaks of DNA damage induced by OGD/R in H9c2 cells in a dose-dependent manner. Furthermore, we investigated the molecular mechanisms and demonstrated that propofol inhibited forkhead box O 1 (FoxO1) phosphorylation and increased FoxO1 nuclear translocation through inhibition of protein kinase B (Akt) and adenosine 5’-monophosphate-activated protein kinase (AMPK) pathways. The protective effects of propofol against oxidative stress-induced DNA damage were reversed by silencing FoxO1. Taken together, our results suggest that oxidative stress aggravates DNA damage and apoptosis in H9C2 cells, which can be reversed by propofol via FoxO1 nuclear translocation.https://www.frontiersin.org/article/10.3389/fphys.2019.00223/fullpropofoloxygen glucose deprivation and reperfusionROSDNA damageFoxO1 |
| spellingShingle | Dandan Zhou Jinqiang Zhuang Yihui Wang Dandan Zhao Lidong Zhao Shun Zhu Shun Zhu Jinjun Pu Ming Yin Hongyu Zhang Zejian Wang Jiang Hong Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells Frontiers in Physiology propofol oxygen glucose deprivation and reperfusion ROS DNA damage FoxO1 |
| title | Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells |
| title_full | Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells |
| title_fullStr | Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells |
| title_full_unstemmed | Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells |
| title_short | Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells |
| title_sort | propofol alleviates dna damage induced by oxygen glucose deprivation and reperfusion via foxo1 nuclear translocation in h9c2 cells |
| topic | propofol oxygen glucose deprivation and reperfusion ROS DNA damage FoxO1 |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00223/full |
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