Upregulation of UCP2 Expression Protects against LPS-Induced Oxidative Stress and Apoptosis in Cardiomyocytes.

Hu Hao,Jinda Huang,Qiyi Zeng,Yue Ding,Wanwan Peng,Juanjuan Lyu,Sitao Li,Yijun Zheng,Junliang Zhang,Yu Yao

doi:10.1155/2019/2758262

Abstract

Uncoupling protein 2 (UCP2) has a cardioprotective role under septic conditions, but the underlying mechanism remains unclear. This study aimed at investigating the effects of UCP2 on the oxidative stress and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS). First, LPS increased UCP2 expression in cardiomyocytes in a time-dependent manner. LPS increased the production of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and malondialdehyde (MDA) and decreased the level of superoxide dismutase (SOD). However, UCP2 knockdown increased the LPS-induced cardiac injury and oxidative stress. In addition, LPS damaged the mitochondrial ultrastructure and led to the disruption of mitochondrial membrane potential (MMP), as well as the release of mitochondrial cytochrome c. UCP2 knockdown aggravated mitochondrial injury and the release of mitochondrial cytochrome c. LPS increased the protein levels of Bax and cleaved-caspase-3, decreased the protein level of Bcl-2, and upregulated the protein level of mitogen-activated protein kinase. However, upon UCP2 knockdown, the protein levels of Bax and cleaved-caspase-3 increased even further, and the protein level of Bcl-2 was further decreased. The protein level of phosphorylated p38 was also further enhanced. Thus, UCP2 protects against LPS-induced oxidative stress and apoptosis in cardiomyocytes.

Highlights

Sepsis is the host response to infection and a major cause of mortality worldwide [1,2,3]
We investigated the effects of LPS treatment on Uncoupling protein 2 (UCP2) and UCP3 expression in neonatal rat cardiomyocytes
We focus on the role of UCP2 in cardiomyocytes

Summary

Introduction

Sepsis is the host response to infection and a major cause of mortality worldwide [1,2,3]. Sepsis patients experiencing myocardial dysfunction have a high mortality of up to 70% [6]. Mitochondrial oxidative stress and apoptosis have been demonstrated to play a critical role in sepsis-induced myocardial dysfunction (SIMD) [7,8,9]. Generation of reactive oxygen species (ROS) associated with sepsis is known as one of the most deleterious causes of oxidative damage. Excessive production of mitochondrial ROS is responsible for oxidative stress and correlates with the development of SIMD due to the effects on myocardial cells [15,16,17]. Excessive harmful ROS could trigger mitochondrial oxidative damage and a series of apoptotic events in cardiomyocytes, which eventually lead to cell

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