title: NOD2 mediates isoflurane preconditioning-induced protection of myocardial injury.
abstract: Anesthetic cardioprotection reduces myocardial infarct size following ischemia-reperfusion injury. However, the underlying mechanisms that drive ischemia-reperfusion injury in cardiomyocytes remain unclear. In this study, we report that isoflurane, a commonly used inhaled anesthetic, can protect cardiomyocytes from anoxia/reoxygenation injury by a nucleotide binding oligomerization domain containing 2 (NOD2)-dependent mechanism. The results showed that isoflurane increased cell viability, and decreased autophagosome generation in primary cardiomyocytes under anoxia/reoxygenation conditions. In addition, western blot revealed that isoflurane reduces the expression of NOD2. Overexpression of NOD2 is accompanied by an increased expression of autophagy-related genes, decreased cell viability, and enhanced expression of phosphorylation p38-mitogen-activated protein kinase (p38MAPK), while NOD2 knockdown exerted the opposite effect. Following preconditioning with SB203580, a p38MAPK inhibitor, the inhibitory effect of isoflurane on cardiomyocytes autophagy was further enhanced, which suggests that p38MAPK is involved in the mechanism of cardioprotection provided by isoflurane. These findings reveal a novel mechanism underlying isoflurane-afford protection of myocardial injury.
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of anesthesiology, General hospital of Tianjin medical university, Tianjin 300052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Yan
authors.affiliation: Department of anesthesiology, the Central Hospital of Enshi Autonomous Prefecture, Enshi 445000, China.
authors.forename: Banglin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Sun
authors.affiliation: Tianjin medical university graduate school; Department of anesthesiology, Affiliated Hospital of Logistics University of PAP, Tianjin 300162, China. Electronic address: jiegaojg@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D007530:Isoflurane / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D007530:Isoflurane; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Autophagy; Cardiomyocytes; Nucleotide binding oligomerization domain containing 2; p38MAPK