Protective role of STVNa in myocardial ischemia reperfusion injury by inhibiting mitochondrial fission.

Xiaoou Sun,Yanxiang Xie,Lijie Huang,Wen Tan,Xingjuan Shi,Yingying Yang

doi:10.18632/oncotarget.22969

Abstract

It has been reported that isosteviol, a widely known sweeteners, can protect against myocardial ischemia-reperfusion (IR) injury in isolated guinea pig heart. Here, we aim to confirm the cardioprotective effect of its sodium salt, isosteviol sodium (STVNa), against IR injury and its potential molecular mechanism in H9c2 cardiomyocytes. STVNa significantly improved cell viability, restored mitochondrial membrane potential, decreased cellular reactive oxygen species generation, and inhibited cell apoptosis. Furthermore, STVNa treatment changed the morphology of mitochondria from fragmented, discontinuous forms to normal elongated, tubular forms. Cyto-immunofluorescence and western blot analysis revealed that STVNa inhibited mitochondrial fission proteins dynamin-related protein 1 (Drp1), and mitochondrial fission 1 (Fis1), thus plays a key role in cardioprotection. These findings, for the first time, suggest that STVNa can protect against myocardial IR injury through reverse mitochondrial fission.

Highlights

Isosteviol, is the acid hydrolysate product of stevioside, a widely known sweeteners
Cyto-immunofluorescence and western blot analysis revealed that STVNa inhibited mitochondrial fission proteins dynamin-related protein 1 (Drp1), and mitochondrial fission 1 (Fis1), plays a key role in cardioprotection
It has been shown that dynamin-related protein 1 (Drp1), and mitochondrial fission 1 (Fis1) play key roles in this process [10]

Summary

Introduction

Isosteviol, is the acid hydrolysate product of stevioside, a widely known sweeteners. The pathophysiology of myocardial reperfusion injury can induce arrhythmias, myocardial stunning, oxidative stress, intracellular Ca2+ overload, and mitochondrial permeability transition pore (mPTP) opening [8]. Processes involved in myocardial cell IRinjury include inflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress, and cell apoptosis [8, 9]. Mitochondria are important regulators of cell growth, and are highly dynamic organelles involved in fusion and fission in response to ischemia or other types of oxidative stress [9]. When undergoing IR-injury the mitochondrial permeability transition pore opens, mitochondria dynamic balance would be lost, lead to changes in morphology and the mitochondria are fragmented and discontinuous. Changes in mitochondria morphology have an impact on mitochondrial membrane potential (ψm), impair the redox buffer system and induce reactive oxygen species (ROS) production [11]. We found that isosteviol sodium (STVNa), the sodium salt of isosteviol protects www.impactjournals.com/oncotarget

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