Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats
Mitochondrial autophagy is involved in myocardial protection of sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that deferoxamine (DFO) could activate impaired HIF-1α in diabetic stat...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00006/full |
| _version_ | 1818338000521658368 |
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| author | Long Yang Peng Xie Jianjiang Wu Jin Yu Xin Li Haiping Ma Tian Yu Haiying Wang Jianrong Ye Jiang Wang Hong Zheng |
| author_facet | Long Yang Peng Xie Jianjiang Wu Jin Yu Xin Li Haiping Ma Tian Yu Haiying Wang Jianrong Ye Jiang Wang Hong Zheng |
| author_sort | Long Yang |
| collection | DOAJ |
| description | Mitochondrial autophagy is involved in myocardial protection of sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that deferoxamine (DFO) could activate impaired HIF-1α in diabetic state to restore the cardioprotective of sevoflurane, while the specific mechanism is unclear. This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of sevoflurane postconditioning cardioprotection in diabetic state. Ischemia/reperfusion (I/R) model was established by ligating the anterior descending coronary artery and sevoflurane was administered at the first 15 min of reperfusion. Myocardial infarct size, mitochondrial ultrastructure and autophagosome, ATP content, mitochondrial membrane potential, ROS production, HIF-1α, BNIP3, LC3B-II, Beclin-1, P62, LAMP2 protein expression were detected 2 h after reperfusion, and cardiac function was evaluated by ultrasound at 24 h after reperfusion. Our results showed that with DFO treatment, SPostC up-regulated the expression of HIF-1α and BNIP3, thus reduced the expression of key autophagy proteins LC3B-II, Beclin-1, p62, and increased the expression of LAMP2. Furthermore, it reduced the accumulation of autophagosomes and ROS production, increased the content of ATP, and stabilized the membrane potential. Finally, the myocardial infarction size was reduced and cardiac function was improved. Taken together, DFO treatment combined with SPostC could alleviate myocardial ischemia reperfusion injury in diabetic rats by restoring and promoting HIF-1/BNIP3-mediated mitochondrial autophagy. |
| first_indexed | 2024-12-13T15:04:09Z |
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| id | doaj.art-36c608ceaf2945d09c12e5a7a4e0263e |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T15:04:09Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-36c608ceaf2945d09c12e5a7a4e0263e2022-12-21T23:41:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-02-011110.3389/fphar.2020.00006503051Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK RatsLong Yang0Peng Xie1Jianjiang Wu2Jin Yu3Xin Li4Haiping Ma5Tian Yu6Haiying Wang7Jianrong Ye8Jiang Wang9Hong Zheng10Department of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Department of Anesthesiology, Zunyi Medical College, Zunyi, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Anesthesiology, Chongqing Health Center for Women and Children, Chongqing, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Department of Anesthesiology, Zunyi Medical College, Zunyi, ChinaGuizhou Key Laboratory of Anesthesia and Organ Protection, Department of Anesthesiology, Zunyi Medical College, Zunyi, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaMitochondrial autophagy is involved in myocardial protection of sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that deferoxamine (DFO) could activate impaired HIF-1α in diabetic state to restore the cardioprotective of sevoflurane, while the specific mechanism is unclear. This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of sevoflurane postconditioning cardioprotection in diabetic state. Ischemia/reperfusion (I/R) model was established by ligating the anterior descending coronary artery and sevoflurane was administered at the first 15 min of reperfusion. Myocardial infarct size, mitochondrial ultrastructure and autophagosome, ATP content, mitochondrial membrane potential, ROS production, HIF-1α, BNIP3, LC3B-II, Beclin-1, P62, LAMP2 protein expression were detected 2 h after reperfusion, and cardiac function was evaluated by ultrasound at 24 h after reperfusion. Our results showed that with DFO treatment, SPostC up-regulated the expression of HIF-1α and BNIP3, thus reduced the expression of key autophagy proteins LC3B-II, Beclin-1, p62, and increased the expression of LAMP2. Furthermore, it reduced the accumulation of autophagosomes and ROS production, increased the content of ATP, and stabilized the membrane potential. Finally, the myocardial infarction size was reduced and cardiac function was improved. Taken together, DFO treatment combined with SPostC could alleviate myocardial ischemia reperfusion injury in diabetic rats by restoring and promoting HIF-1/BNIP3-mediated mitochondrial autophagy.https://www.frontiersin.org/article/10.3389/fphar.2020.00006/fullmitochondrial autophagysevoflurane postconditioningdiabetesischemia-reperfusionhypoxia-inducible factor-1 |
| spellingShingle | Long Yang Peng Xie Jianjiang Wu Jin Yu Xin Li Haiping Ma Tian Yu Haiying Wang Jianrong Ye Jiang Wang Hong Zheng Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats Frontiers in Pharmacology mitochondrial autophagy sevoflurane postconditioning diabetes ischemia-reperfusion hypoxia-inducible factor-1 |
| title | Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats |
| title_full | Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats |
| title_fullStr | Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats |
| title_full_unstemmed | Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats |
| title_short | Deferoxamine Treatment Combined With Sevoflurane Postconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Restoring HIF-1/BNIP3-Mediated Mitochondrial Autophagy in GK Rats |
| title_sort | deferoxamine treatment combined with sevoflurane postconditioning attenuates myocardial ischemia reperfusion injury by restoring hif 1 bnip3 mediated mitochondrial autophagy in gk rats |
| topic | mitochondrial autophagy sevoflurane postconditioning diabetes ischemia-reperfusion hypoxia-inducible factor-1 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00006/full |
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