EEF1A2 accelerates the protein translation of chemokine in rat myocardial cells induced by ischemia-reperfusion.

How to reduce the damage caused by myocardial ischemia-reperfusion (IR) in a timely manner to save patients' lives is still a great clinical challenge. Although dexmedetomidine (DEX) has been reported to protect the myocardium, the regulatory mechanism of gene translation responding to IR injury and DEX protection is poorly understood. In this study, IR rat model with DEX and the antagonist yohimbine (YOH) pretreatment were established, and RNA sequencing was carried out to seek the important regulators in differential expressed genes. A series of cytokines and chemokine as well as eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) were induced by IR compared to control and compromised by DEX pretreatment compared to IR, then reversed by YOH. Immunoprecipitation was conducted to identify that peroxiredoxin 1 (PRDX1) interacted with EEF1A2 and contributed to the recruitment of EEF1A2 on mRNA molecules of cytokines and chemokine. Knockdown of PRDX1 could weaken the enhancive effect of EEF1A2 for gene translation of IL6, CXCL2 and CXCL11 under the IR condition, and indeed reduce cell apoptosis of cardiomyocytes. We also determined that the RNA motif "USCAGDCU" at 5' UTR could be particularly recognized by PRDX1. Destruction of this motif at the 5' UTR of IL6, CXCL2 and CXCL11 by CRISPR-CAS9 could result in the loss occupancies of EEF1A2 and PRDX1 on the mRNA of these three genes. Our observations showed the importance of PRDX1 in the reasonable control of cytokine and chemokine expression to prevent excessive inflammatory response to cell damage.