Aims: Our previous studies have shown that N-n-butyl haloperidol iodide (F₂) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca²⁺ overload. The present study is to test the hypothesis that the protective effects of F₂ on myocardial I/R injury is mediated by downregulating Egr-1 expression. Methods: The Sprague–Dawley rat myocardial I/R model and cardiomyocyte hypoxia/reoxygenation (H/R) model were established. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and myocardial I/R injury was investigated. Hemodynamic parameters, myeloperoxidase (MPO), cardiac troponin I (cTnI) and tumor necrosis factor-α (TNF-α) were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Egr-1 mRNA and protein expressions were examined by Northern-blot and Western-blot analyses. Results: Treatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of myocardial tissues and cells. Meanwhile, treatment with F₂ significantly inhibited the overexpression of Egr-1 mRNA and protein in myocardial tissues and cells. Consistent with downregulation of Egr-1 expression by F₂, inflammation and other damages were significantly relieved evidenced by the amelioration of hemodynamics, the reduction in myocardial MPO activity as well as the decrease in leakage of cTnI and release of TNF-α from cardiomyocyte. Conclusions: These results suggested that the overexpression of Egr-1 was causative in myocardial I/R or H/R injury, and F₂ could protect myocardial tissues and cells from I/R or H/R injury, which was largely due to the inhibition of Egr-1 overexpresssion.

Aims: Our previous studies have shown that myocardial ischemia-reperfusion (I/R) injury is related closely with early growth response (Egr)-1 overexpression. The present study is to confirm thoroughly the effects of Egr-1 on the occurrance and development of myocardial I/R injury. Methods: The Sprague-Dawley rat myocardial I/R model and cultured cardiomyocyte hypoxia-reoxygenation (H/R) model were established. The synthesized Egr-1 antisense oligodeoxyribonucleotide (AS-ODN) was transfected into myocardial tissues and cells. Hemodynamic parameters, myeloperoxidase (MPO), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), morphology, spontaneous beat and cell viability were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Results: In vivo, Egr-1 AS-ODN significantly attenuated injury and inflammation of myocardial tissues caused by I/R evidenced by the amelioration of hemodynamics and the reduction in MPO activity. In vitro, Egr-1 AS-ODN significantly relieved injury and inflammation of cultured cardiomyocyte caused by H/R evidenced by the improvement in morphology, structure and beat as well as the decrease in leakage of cTnI and release of TNF-α from cultured cardiomyocyte. Conclusions: These data suggest that Egr-1 plays a vital role in the pathogenesis of myocardial I/R injury and Egr-1 AS-ODN could protect the myocardium from I/R injury.

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Small ubiquitin-like modifier (SUMO)-based post-translational modification, an important cellular regulatory mechanism that participates in various cell growth processes, can be modified by transcription factors, enzyme and receptor activity, proteasome degradation, protein aggregation, chromatin targeting and proteinprotein interactions (Harding & Greenberg, 2016). It is an important class of ubiquitin-like proteins that can be coupled to a variety of cellular proteins to maintain genome integrity and resist genotoxicity. Four SUMO isoforms have been identified in mammals:

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