Curcumin Protects Neonatal Rat Cardiomyocytes against High Glucose-Induced Apoptosis via PI3K/Akt Signalling Pathway.

Wei Yu,Qing Min,Chao Liu,Huirong Sun,Zhiqiang Ke,Cairong Li,Wenliang Zha

doi:10.1155/2016/4158591

Abstract

The function of curcumin on NADPH oxidase-related ROS production and cardiac apoptosis, together with the modulation of protein signalling pathways, was investigated in cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were exposed to 30 mmol/L high glucose with or without curcumin. Cell viability, apoptosis, superoxide formation, the expression of NADPH oxidase subunits, and potential regulatory molecules, Akt and GSK-3β, were assessed in cardiomyocytes. Cardiomyocytes exposure to high glucose led to an increase in both cell apoptosis and intracellular ROS levels, which were strongly prevented by curcumin treatment (10 μM). In addition, treatment with curcumin remarkably suppressed the increased activity of Rac1, as well as the enhanced expression of gp91phox and p47phox induced by high glucose. Lipid peroxidation and SOD were reversed in the presence of curcumin. Furthermore, curcumin treatment markedly inhibited the reduced Bcl-2/Bax ratio elicited by high glucose exposure. Moreover, curcumin significantly increased Akt and GSK-3β phosphorylation in cardiomyocytes treated with high glucose. In addition, LY294002 blocked the effects of curcumin on cardiomyocytes exposure to high glucose. In conclusion, these results demonstrated that curcumin attenuated high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH-mediated oxidative stress and this protective effect is most likely mediated by PI3K/Akt-related signalling pathway.

Highlights

Diabetes mellitus (DM) is becoming a global health problem that is afflicting millions of people
To ascertain the role of curcumin in cell survival, we examined the viability of primary cultured neonatal rat cardiomyocytes incubated with different doses of curcumin for 24 h using a CCK-8 assay
In the cardiomyocytes exposed to high glucose, curcumin treatment increased cell viability in a dose-dependent manner

Summary

Introduction

Diabetes mellitus (DM) is becoming a global health problem that is afflicting millions of people. According to the investigation conducted by the International Diabetes Federation (IDF), the incidence of DM is rapidly increasing and the total number of people with DM will reach 592 million in 2035 [1]. Studies have indicated that diabetic people have a 2- to 5-fold increased risk of developing heart failure [2] and that more than 50%–80% of diabetic patients die from diabetic cardiovascular complications [3]. Numerous studies utilizing experimental animal models and clinical diabetes patients reported that diabetes enhances cardiomyocyte apoptosis in animals and in patients [6, 7]. Cardiomyocyte apoptosis can cause a loss of cardiac contractile muscle tissue, which eventually leads to left ventricular remodeling [9]

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Conclusion