Y Kou1, W-T Zheng, Y-R Zhang. 1. Department of Cardiovascular Medicine, Binzhou People's Hospital, BinZhou, Shandong, China. ky7171@sina.com.
Abstract
OBJECTIVE: Myocardial disorders caused by ischemia/reperfusion (IR) continue to be among the most frequent causes of debilitating disease and death. The contribution of cellular metabolism through the production of metabolic intermediates during IR has been increasingly investigated. MATERIALS AND METHODS: In this study, by using a rat IR injury model, we reported that the expression of microRNA miR-23 was induced by IR. In contrast, the glutamine metabolism was suppressed during IR. The glutamate, glutamine dehydrogenase activity, α-ketoglutarate, and glutaminase (GLS) mRNA expression were significantly decreased by IR. Moreover, the pretreatment of glutamine could protect the myocardium from IR injury. RESULTS: From microRNA target prediction analysis and results of luciferase assay, we found that miR-23 could directly target the 3'UTR of GLS. Finally, we demonstrated that inhibition of miR-23 protected myocardial function from IR through the restoration of glutamine metabolism. CONCLUSIONS: This study reveals that inhibition of miR-23 renders protective effects on rat IR injury, highlighting the importance of miR-23 and glutamine metabolism during IR, and suggests a potentially clinical benefit.
OBJECTIVE:Myocardial disorders caused by ischemia/reperfusion (IR) continue to be among the most frequent causes of debilitating disease and death. The contribution of cellular metabolism through the production of metabolic intermediates during IR has been increasingly investigated. MATERIALS AND METHODS: In this study, by using a rat IR injury model, we reported that the expression of microRNA miR-23 was induced by IR. In contrast, the glutamine metabolism was suppressed during IR. The glutamate, glutamine dehydrogenase activity, α-ketoglutarate, and glutaminase (GLS) mRNA expression were significantly decreased by IR. Moreover, the pretreatment of glutamine could protect the myocardium from IR injury. RESULTS: From microRNA target prediction analysis and results of luciferase assay, we found that miR-23 could directly target the 3'UTR of GLS. Finally, we demonstrated that inhibition of miR-23 protected myocardial function from IR through the restoration of glutamine metabolism. CONCLUSIONS: This study reveals that inhibition of miR-23 renders protective effects on rat IR injury, highlighting the importance of miR-23 and glutamine metabolism during IR, and suggests a potentially clinical benefit.