The protective effect of allicin on myocardial ischemia-reperfusion by inhibition of Ca2+ overload-induced cardiomyocyte apoptosis via the PI3K/GRK2/PLC-γ/IP3R signaling pathway.

Tong Gao,Xinyi Deng,Mingjing Shao,Peng Yang,Jiangquan Liao,Hong Jiang,Dongliang Fu,Xianlun Li,Mengru Liu

doi:10.18632/aging.203375

Abstract

Purpose: To investigate the protective effect and mechanism of allicin on myocardial ischemia-reperfusion (MI/R) injury.Methods: We investigated the mechanisms by which allicin attenuated the MI/R injury by focusing on phosphoinositide 3-kinase, G protein coupled receptor kinases 2, phospholipase Cγ and cardiomyocyte apoptosis. Sixty male mice were randomly assigned into three groups: repeated MI/R (model), sham-operated (control), and MI/R+ allicin group (allicin). Ultrasound examination was used to examine the cardiac function. Masson staining was used to evaluate the myocardial infarct area. TUNEL assay was performed to examine the anti-apoptotic effect of allicin. Differentially expressed genes (DEGs) and pathways were analyzed by mRNA microarray analysis. Immunofluorescence staining and western blot were carried out to detect the effect of allicin on the PI3K. A pan-PLC activator, m-3M3FBS, was applied to investigate whether allicin induced cardiomyocyte apoptosis was via the GRK2/PLC/IP3R signaling pathway.Results: Masson staining and the TUNEL assay revealed that allicin reduced infarct size and played an anti-apoptotic role in M/IR. Ultrasound examination revealed that allicin improved cardiac function after M/IR injury. Gene ontology analysis indicated that the calcium signaling pathway and PI3KCA(PI3K) were selected. Immunofluorescence staining and western blot exposed that PI3K was activated by allicin during MI/R injury. Fura-2AM staining revealed that the PI3K -mediated GRK2/PLC-γ/IP3R pathway may be involved in the protective effect of allicin on MI/R injury.Conclusions: Allicin has a protective effect on MI/R injury. This effect might be associated with the inhibition of Ca2+ overload-induced apoptosis and the inhibition of the PI3K -mediated GRK2/PLC-γ/IP3R signaling pathway.

Highlights

Myocardial ischemia-reperfusion (MI/R) injury is a common disease and continues to have high morbidity and mortality in the world [1, 2]
As we demonstrated that allicin could repress cardiomyocyte apoptosis and activate PI3K, which caused the inhibition of GRK2, PLC-γ, and IP3R induced Ca2+ release, we examined the potential mechanism involved
These results suggested that the protective effect of allicin on MI/R injury by PI3K -mediated was via GRK2/PLC-γ/IP3R pathway

Summary

Introduction

Myocardial ischemia-reperfusion (MI/R) injury is a common disease and continues to have high morbidity and mortality in the world [1, 2]. MI/R injury is considered reperfusion injury in patients who suffered from cardiovascular surgery and may develop into some severe cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure [3,4,5]. Active cardiomyocyte death, is recognized as the primary cause of MI/R [9]. Intracellular Ca2+ overload is considered to be a significant cause of ischemic myocardial cell injury and apoptosis [10, 11]. Various studies have confirmed that intracellular calcium overloading could lead to mitochondrial dysfunction, which is crucial for facilitating cardiomyocyte apoptosis in MI/R injury [12]. It is urgent to explore some antiapoptotic pretreatments for ischemia diseases

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Conclusion