Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis

Lei Yang,Lanjie Lei,Xiangguo Wang,Gaopeng Guan,Jianyun Liu,Lingling Cao

doi:10.1042/bsr20190225

Abstract

Palmitic acid (PA) is the most common saturated long-chain fatty acid that causes damage to heart muscle cells. However, the molecular mechanism of PA toxicity in myocardial cells is not fully understood. In the present study, we explored the effects of PA on proliferation and apoptosis of H9c2 cardiomyocytes, and uncovered the signaling pathways involved in PA toxicity. Our study revealed induction of both oxidative and endoplasmic reticulum (ER) stresses and exacerbation of apoptosis in PA-treated H9c2 cells. Inhibition of oxidative stress by N-acetylcysteine (NAC) reduced apoptosis and decreased ER stress in PA-treated H9c2 cells. Moreover, inhibition of ER stress by 4-phenyl butyric acid decreased apoptosis and attenuated oxidative stress. In summary, the present study demonstrated that oxidative stress coordinates with ER stress to play important roles in PA-induced H9c2 cell apoptosis.

Highlights

Diets rich in high fat foods, especially saturated fats, cause obesity, leading to serious health problems, such as type 2 diabetes and lipotoxic cardiomyopathy [1]
The results showed that Palmitic acid (PA) decreased cell viability in a dose-dependent manner from 200 to 800 μM concentrations compared with the control group, and the IC50 value was approximately 400 μM (Figure 1A, P=0.0032)
Our results showed that endoplasmic reticulum (ER) stress was active and expression of CCAAT/enhancer binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) was up-regulated at mRNA and proteins levels in a dose-dependent manner from 200 to 800 μM concentrations compared with the control group at 24 h (Figures 3A,B and Supplementray Figure S1b,c)

Summary

Introduction

Diets rich in high fat foods, especially saturated fats, cause obesity, leading to serious health problems, such as type 2 diabetes and lipotoxic cardiomyopathy [1]. Palmitic acid (PA), the most common saturated long-chain fatty acid, triggers apoptosis in many cell types including cardiomyocytes [4]. Cardiomyocyte apoptosis leads to myocardial injury and results in heart dysfunction to some extent [5]. Any physiological or pathological perturbation can disrupt ER homeostasis and cause accumulation of unfolded or misfolded proteins in the ER lumen, resulting in ER stress [9]. Glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) are both activated by the ER stress response [8]. When the unfolded protein response fails to manage misfolded and unfolded proteins, the stress triggers apoptosis [9]

Methods

Results

Conclusion