Cucurbitacin I Protects H9c2 Cardiomyoblasts against H2O2-Induced Oxidative Stress via Protection of Mitochondrial Dysfunction.

Dong Kwon Yang,Shang-Jin Kim

doi:10.1155/2018/3016382

Dong Kwon Yang, Shang-Jin Kim

Open Access

https://doi.org/10.1155/2018/3016382

Copy DOI

Abstract

Cucurbitacin I, a triterpenoid natural compound, exhibits various pharmacological properties, including anticancer, anti-inflammatory, and hepatoprotective properties. However, antioxidant effects of cucurbitacin I in cardiac cells are currently unknown. In the present study, we assessed the preventive effects of cucurbitacin I against the oxidative stress in H9c2 cardiomyoblasts. To evaluate antioxidant effects of cucurbitacin I in H9c2 cardiomyoblasts, H2O2-treated H9c2 cells were pretreated with various concentrations of the cucurbitacin I. Cell viability, reactive oxygen species (ROS) production, and apoptosis were determined to elucidate the protective effects of cucurbitacin I against H2O2-induced oxidative stress in H9c2 cells. In addition, we assessed the mitochondrial functions and protein expression levels of mitogen-activated protein kinases (MAPKs). Cucurbitacin I prevented the cells against cell death and ROS production and elevated the antioxidant protein levels upon oxidative stress. Furthermore, cucurbitacin I preserved the mitochondrial functions and inhibited the apoptotic responses in H2O2-treated cells. Cucurbitacin I also suppressed the activation of MAPK proteins (extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38). Collectively, cucurbitacin I potentially protects the H9c2 cardiomyoblasts against oxidative stress and further suggests that it can be utilized as a therapeutic agent for the prevention of oxidative stress in cardiac injury.

Highlights

Ischemic heart disease (IHD), known as coronary artery disease, is the most common type of cardiovascular disease, which occurred by reduced blood supply to the heart [1]
All cucurbitacin I (Cu I)-treated cells were shown that the protein expression of antioxidant proteins, including superoxide dismutase- (SOD-)1, catalase, and glutathione peroxidase (GPx), did not change compared with those in control cells (Figures 1(e) and 1(f))
Pretreatment with 0.1, 0.5, and 1 μM Cu I for 24 h significantly increased the viability of H2O2-treated cells in a dosedependent manner (83.6%, 90.4%, and 110.9% increases in cells pretreated with 0.1, 0.5, and 1 μM Cu I versus H2O2treated cells, resp.) (Figure 2(a)). These results indicate that Cu I prevents the mortality of H9c2 cardiomyoblasts induced by oxidative stress by H2O2 without cytotoxic effects

Summary

Introduction

Ischemic heart disease (IHD), known as coronary artery disease, is the most common type of cardiovascular disease, which occurred by reduced blood supply to the heart [1]. It is the most prevalent cause of death worldwide, especially in developed countries. Accumulating evidences indicate that major pathological events associated with I/R injury are oxidative stress, lipid peroxidation, intracellular calcium overload, and mitochondrial dysfunction [6]. Oxidative stress which causes to accumulation of reactive oxygen species (ROS) plays a major role in the development of cardiac I/R injury [7]. Excessive ROS production leads to increased mitochondrial permeability and in turn induces apoptosis in cardiac cells, which further progresses to the chronic heart failure [8]

Methods

Results

Conclusion