Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy
Myocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.604700/full |
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| author | Tzu-Lin Lee Ming-Hsueh Lee Ming-Hsueh Lee Yu-Chen Chen Yi-Chieh Lee Tsai-Chun Lai Hugo You-Hsien Lin Lee-Fen Hsu Lee-Fen Hsu Hsin-Ching Sung Hsin-Ching Sung Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yuh-Lien Chen |
| author_facet | Tzu-Lin Lee Ming-Hsueh Lee Ming-Hsueh Lee Yu-Chen Chen Yi-Chieh Lee Tsai-Chun Lai Hugo You-Hsien Lin Lee-Fen Hsu Lee-Fen Hsu Hsin-Ching Sung Hsin-Ching Sung Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yuh-Lien Chen |
| author_sort | Tzu-Lin Lee |
| collection | DOAJ |
| description | Myocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fission and mitophagy are essential factors for mitochondrial quality control, but whether they play key roles in cardiac I/R injury remains unknown. New pharmacological or molecular interventions to alleviate reperfusion injury are currently considered desirable therapies. Vitamin D3 (Vit D3) regulates cardiovascular function, but its physiological role in I/R-exposed hearts, especially its effects on mitochondrial homeostasis, remains unclear. An in vitro hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate myocardial I/R injury. H/R treatment significantly reduced H9c2 cell viability, increased apoptosis, and activated caspase 3. In addition, H/R treatment increased mitochondrial fission, as manifested by increased expression of phosphorylated dynein-related protein 1 (p-Drp1) and mitochondrial fission factor (Mff) as well as increased mitochondrial translocation of Drp1. Treatment with the mitochondrial reactive oxygen species scavenger MitoTEMPO increased cell viability and decreased mitochondrial fission. H/R conditions elicited excessive mitophagy, as indicated by increased expression of BCL2-interacting protein 3 (BNIP3) and light chain (LC3BII/I) and increased formation of autolysosomes. In contrast, Vit D3 reversed these effects. In a mouse model of I/R, apoptosis, mitochondrial fission, and mitophagy were induced. Vit D3 treatment mitigated apoptosis, mitochondrial fission, mitophagy, and myocardial ultrastructural abnormalities. The results indicate that Vit D3 exerts cardioprotective effects against I/R cardiac injury by protecting mitochondrial structural and functional integrity and reducing mitophagy. |
| first_indexed | 2024-12-14T16:56:15Z |
| format | Article |
| id | doaj.art-8fa70257bbf440eda3a51077d8a0c2fb |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T16:56:15Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-8fa70257bbf440eda3a51077d8a0c2fb2022-12-21T22:53:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.604700604700Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and MitophagyTzu-Lin Lee0Ming-Hsueh Lee1Ming-Hsueh Lee2Yu-Chen Chen3Yi-Chieh Lee4Tsai-Chun Lai5Hugo You-Hsien Lin6Lee-Fen Hsu7Lee-Fen Hsu8Hsin-Ching Sung9Hsin-Ching Sung10Chiang-Wen Lee11Chiang-Wen Lee12Chiang-Wen Lee13Yuh-Lien Chen14Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDivision of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanDivision of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, TaiwanDepartment of Anatomy, College of Medicine, Chang Gung University, Taoyuan, TaiwanAesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, TaiwanDepartment of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi, TaiwanResearch Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan, TaiwanDepartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanMyocardial infarction is the leading cause of morbidity and mortality worldwide. Although myocardial reperfusion after ischemia (I/R) is an effective method to save ischemic myocardium, it can cause adverse reactions, including increased oxidative stress and cardiomyocyte apoptosis. Mitochondrial fission and mitophagy are essential factors for mitochondrial quality control, but whether they play key roles in cardiac I/R injury remains unknown. New pharmacological or molecular interventions to alleviate reperfusion injury are currently considered desirable therapies. Vitamin D3 (Vit D3) regulates cardiovascular function, but its physiological role in I/R-exposed hearts, especially its effects on mitochondrial homeostasis, remains unclear. An in vitro hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate myocardial I/R injury. H/R treatment significantly reduced H9c2 cell viability, increased apoptosis, and activated caspase 3. In addition, H/R treatment increased mitochondrial fission, as manifested by increased expression of phosphorylated dynein-related protein 1 (p-Drp1) and mitochondrial fission factor (Mff) as well as increased mitochondrial translocation of Drp1. Treatment with the mitochondrial reactive oxygen species scavenger MitoTEMPO increased cell viability and decreased mitochondrial fission. H/R conditions elicited excessive mitophagy, as indicated by increased expression of BCL2-interacting protein 3 (BNIP3) and light chain (LC3BII/I) and increased formation of autolysosomes. In contrast, Vit D3 reversed these effects. In a mouse model of I/R, apoptosis, mitochondrial fission, and mitophagy were induced. Vit D3 treatment mitigated apoptosis, mitochondrial fission, mitophagy, and myocardial ultrastructural abnormalities. The results indicate that Vit D3 exerts cardioprotective effects against I/R cardiac injury by protecting mitochondrial structural and functional integrity and reducing mitophagy.https://www.frontiersin.org/articles/10.3389/fphar.2020.604700/fullcardiac ischemia/reperfusionmitochondrial fissionvitamin D3apoptosismitophagy |
| spellingShingle | Tzu-Lin Lee Ming-Hsueh Lee Ming-Hsueh Lee Yu-Chen Chen Yi-Chieh Lee Tsai-Chun Lai Hugo You-Hsien Lin Lee-Fen Hsu Lee-Fen Hsu Hsin-Ching Sung Hsin-Ching Sung Chiang-Wen Lee Chiang-Wen Lee Chiang-Wen Lee Yuh-Lien Chen Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy Frontiers in Pharmacology cardiac ischemia/reperfusion mitochondrial fission vitamin D3 apoptosis mitophagy |
| title | Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy |
| title_full | Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy |
| title_fullStr | Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy |
| title_full_unstemmed | Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy |
| title_short | Vitamin D Attenuates Ischemia/Reperfusion-Induced Cardiac Injury by Reducing Mitochondrial Fission and Mitophagy |
| title_sort | vitamin d attenuates ischemia reperfusion induced cardiac injury by reducing mitochondrial fission and mitophagy |
| topic | cardiac ischemia/reperfusion mitochondrial fission vitamin D3 apoptosis mitophagy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.604700/full |
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