NOD2 mediates isoflurane preconditioning-induced protection of myocardial injury

Autor: Cheng Yang, Yiqing Ren, Nuo Yan, Jinchao Sun, Jie Gao, Banglin Wu, Hui Li, Yang Jiao
Rok vydání: 2017
Předmět:
Zdroj: Neuroscience Letters. 637:154-160
ISSN: 0304-3940
DOI: 10.1016/j.neulet.2016.11.031
Popis: 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.
Databáze: OpenAIRE