Dexmedetomidine attenuates myocardial ischemia-reperfusion injury via inhibiting ferroptosis by the cAMP/PKA/CREB pathway

• Published in: Molecular and cellular probes Vol. 68; p. 101899
• Main Authors: Ma, Xiaojing, Xu, Jia, Gao, Nan, Tian, Jun, Song, Tieying
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2023; Elsevier
• Subjects: Apoptosis; cAMP; cAMP/PKA/CREB pathway; Cyclic AMP Response Element-Binding Protein - metabolism; Cyclic AMP Response Element-Binding Protein - pharmacology; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic AMP-Dependent Protein Kinases - pharmacology; Dexmedetomidine; Dexmedetomidine - pharmacology; Ferroptosis; Humans; Ischemia-reperfusion injury; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Ferroptosis; Ischemia-reperfusion injury; cAMP/PKA/CREB pathway; cAMP; Dexmedetomidine
• ISSN: 0890-8508; 1096-1194
• DOI: 10.1016/j.mcp.2023.101899

This study is to investigate the effects of dexmedetomidine on myocardial ischemia-reperfusion (I/R) injury and its molecular mechanisms. H9c2 cell injury model was constructed by the hypoxia/normoxia (H/R) conditions. Besides, cAMP response element-binding protein (CREB) overexpression and knockdown cell lines were constructed. Cell viability was determined by cell-counting kit 8. Biochemical assays were used to detect oxidative stress-related biomarkers, cell apoptosis, and ferroptosis-related markers. Our results showed that dexmedetomidine's protective effects on H/R-induced cell damage were reversed by the inhibition of protein kinase A (PKA), CREB, and extracellular signal regulated kinase 1/2 (ERK1/2). Treatment of dexmedetomidine ameliorated oxidative stress in the cardiomyocytes induced by H/R, whereas inhibition of PKA, CREB, or ERK1/2 reversed these protective effects. Cell death including cell necrosis, apoptosis, and ferroptosis was found in the cells under H/R insult. Interestingly, targeting CREB ameliorated ferroptosis and oxidative stress in these cells. In conclusion, dexmedetomidine attenuates myocardial I/R injury by suppressing ferroptosis through the cAMP/PKA/CREB signaling pathway. •Treatment of DEX ameliorated oxidative stress in the cardiomyocytes induced by H/R.•Cell necrosis, apoptosis, and ferroptosis were also found in the I/R injury cell model.•DEX attenuated myocardial I/R injury by suppressing ferroptosis through the cAMP/PKA/CREB pathway.