PMID- 34938777
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231002
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 8
DP  - 2021
TI  - Diazoxide Post-conditioning Activates the HIF-1/HRE Pathway to Induce Myocardial 
      Protection in Hypoxic/Reoxygenated Cardiomyocytes.
PG  - 711465
LID - 10.3389/fcvm.2021.711465 [doi]
LID - 711465
AB  - Background: Previous studies have shown that diazoxide can protect against 
      myocardial ischemia-reperfusion injury (MIRI). The intranuclear hypoxia-inducible 
      factor-1 (HIF-1)/hypoxia-response element (HRE) pathway has been shown to 
      withstand cellular damage caused by MIRI. It remains unclear whether diazoxide 
      post-conditioning is correlated with the HIF-1/HRE pathway in protective effect 
      on cardiomyocytes. Methods: An isolated cardiomyocyte model of 
      hypoxia-reoxygenation injury was established. Prior to reoxygenation, 
      cardiomyocytes underwent post-conditioning treatment by diazoxide, and 
      5-hydroxydecanoate (5-HD), N-(2-mercaptopropionyl)-glycine (MPG), or 
      dimethyloxallyl glycine (DMOG) followed by diazoxide. At the end of 
      reoxygenation, ultrastructural morphology; mitochondrial membrane potential; 
      interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), reactive oxygen 
      species (ROS), and HIF-1alpha levels; and downstream gene mRNA and protein levels 
      were analyzed to elucidate the protective mechanism of diazoxide 
      post-conditioning. Results: Diazoxide post-conditioning enabled activation of the 
      HIF-1/HRE pathway to induce myocardial protection. When the mitoK(ATP) channel 
      was inhibited and ROS cleared, the diazoxide effect was eliminated. DMOG was able 
      to reverse the effect of ROS absence to restore the diazoxide effect. MitoK(ATP) 
      and ROS in the early reoxygenation phase were key to activation of the HIF-1/HRE 
      pathway. Conclusion: Diazoxide post-conditioning promotes opening of the 
      mitoK(ATP) channel to generate a moderate ROS level that activates the HIF-1/HRE 
      pathway and subsequently induces myocardial protection.
CI  - Copyright (c) 2021 Chen, Wang, Cheng, Wang, Deng, Yu, Wang and Zhou.
FAU - Chen, Xi-Yuan
AU  - Chen XY
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
AD  - Department of Anesthesiology, The Xinqiao Hospital of Army Medical University, 
      Chongqing, China.
FAU - Wang, Jia-Qi
AU  - Wang JQ
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
FAU - Cheng, Si-Jing
AU  - Cheng SJ
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
FAU - Deng, Meng-Yuan
AU  - Deng MY
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
FAU - Yu, Tian
AU  - Yu T
AD  - Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of 
      Zunyi Medical University, Guizhou, China.
FAU - Wang, Hai-Ying
AU  - Wang HY
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
FAU - Zhou, Wen-Jing
AU  - Zhou WJ
AD  - Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical 
      University, Guizhou, China.
AD  - Guizhou Key Laboratory of Anesthesia and Organ Protection, Affiliated Hospital of 
      Zunyi Medical University, Guizhou, China.
LA  - eng
PT  - Journal Article
DEP - 20211206
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
EIN - Front Cardiovasc Med. 2023 Sep 13;10:1281995. PMID: 37781299
PMC - PMC8687117
OTO - NOTNLM
OT  - HIF-1/HRE pathway
OT  - cardiomyocytes
OT  - diazoxide
OT  - hypoxic reoxygenation injury
OT  - myocardial protection
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/12/24 06:00
MHDA- 2021/12/24 06:01
PMCR- 2021/01/01
CRDT- 2021/12/23 05:53
PHST- 2021/05/18 00:00 [received]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2021/12/23 05:53 [entrez]
PHST- 2021/12/24 06:00 [pubmed]
PHST- 2021/12/24 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2021.711465 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2021 Dec 6;8:711465. doi: 10.3389/fcvm.2021.711465. 
      eCollection 2021.