Frontiers in Cell and Developmental Biology (Oct 2021)
4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis via Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1
- Xiaoxuan Zhai,
- Xiaoxuan Zhai,
- Xiaoxuan Zhai,
- Xiaoxuan Zhai,
- Xiaoxuan Zhai,
- Xiaoxuan Zhai,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Wenjun Wang,
- Shukun Sun,
- Shukun Sun,
- Shukun Sun,
- Shukun Sun,
- Shukun Sun,
- Shukun Sun,
- Yu Han,
- Yu Han,
- Yu Han,
- Yu Han,
- Yu Han,
- Yu Han,
- Jiaxin Li,
- Jiaxin Li,
- Jiaxin Li,
- Jiaxin Li,
- Jiaxin Li,
- Jiaxin Li,
- Shengchuan Cao,
- Shengchuan Cao,
- Shengchuan Cao,
- Shengchuan Cao,
- Shengchuan Cao,
- Shengchuan Cao,
- Ruochuan Li,
- Ruochuan Li,
- Ruochuan Li,
- Ruochuan Li,
- Ruochuan Li,
- Ruochuan Li,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Tonghui Xu,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Qiuhuan Yuan,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Jiali Wang,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Shujian Wei,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen,
- Yuguo Chen
Affiliations
- Xiaoxuan Zhai
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xiaoxuan Zhai
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xiaoxuan Zhai
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xiaoxuan Zhai
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xiaoxuan Zhai
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Xiaoxuan Zhai
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Wenjun Wang
- Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
- Shukun Sun
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shukun Sun
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shukun Sun
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shukun Sun
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shukun Sun
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shukun Sun
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yu Han
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiaxin Li
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shengchuan Cao
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ruochuan Li
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Tonghui Xu
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qiuhuan Yuan
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Jiali Wang
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shujian Wei
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital, Institute of Emergency and Critical Care Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- Key Laboratory of Emergency and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yuguo Chen
- The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- DOI
- https://doi.org/10.3389/fcell.2021.721795
- Journal volume & issue
-
Vol. 9
Abstract
Background: Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) is abundantly increased during MI/R injury. However, whether 4-HNE induces cardiomyocyte necroptosis during MI/R remains unknown.Methods: To observe the relationship between 4-HNE and necroptosis during MI/R, C57BL/6 mice and aldehyde dehydrogenase 2-transgenic (ALDH2-Tg) mice were both exposed to left anterior descending artery ligation surgery to establish MI/R injury models. For further study, isolated mouse hearts and H9c2 cells were both treated with 4-HNE to elucidate the underlying mechanisms.Results: Necroptosis and 4-HNE were both upregulated in I/R-injured hearts. Cardiomyocyte necroptosis was significantly decreased in I/R-injured hearts from ALDH2-Tg mice as compared with that of wild-type mice. In vitro studies showed that necroptosis was enhanced by 4-HNE perfusion in a time- and concentration-dependent manner. Knockdown of receptor-interacting serine/threonine-protein kinase 1 (RIP1) using small interfering RNA (siRNA) prevented 4-HNE-induced cardiomyocyte necroptosis, manifesting that RIP1 played a key role in the upregulation of cell necroptosis by 4-HNE. Further studies found that 4-HNE reduced the protein degradation of RIP1 by preventing K48-polyubiquitination of RIP1.Conclusion: 4-HNE contributes to cardiomyocyte necroptosis by regulating ubiquitin-mediated proteasome degradation of RIP1.
Keywords
- 4-hydroxynonenal (4-HNE)
- myocardial ischemia – reperfusion injury (MIRI)
- necroptosis
- RIP1 (RIPK1)
- ubiquitination
