Protective Effects of Peroxiredoxin on Hydrogen Peroxide Induced Oxidative Stress and Apoptosis in Cardiomyocytes.
- Author:
Keon Jae PARK
1
;
Yeon Jeong KIM
;
Jeongeun KIM
;
Sang Min KIM
;
Sang Yeub LEE
;
Jang Whan BAE
;
Kyung Kuk HWANG
;
Dong Woon KIM
;
Myeong Chan CHO
Author Information
- Publication Type:Original Article
- Keywords: Peroxiredoxins; Myocytes, cardiac; Oxidative stress; Apoptosis
- MeSH: Animals; Apoptosis; Blotting, Western; Cell Line; Cell Survival; Down-Regulation; Flow Cytometry; Fluorescence; Human Umbilical Vein Endothelial Cells; Hydrogen; Hydrogen Peroxide; Muscle, Smooth, Vascular; Myocytes, Cardiac; Oxidation-Reduction; Oxidative Stress; Peroxiredoxins; Protein Isoforms; Rats; Signal Transduction; Thioredoxin-Disulfide Reductase; Thioredoxins; Up-Regulation
- From:Korean Circulation Journal 2012;42(1):23-32
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: The redox system is an important anti-oxidative system composed of thioredoxin, thioredoxin reductase, and peroxiredoxin (PRx). The fine details of PRx expression and its protective effects in various cells in cardiovascular tissue under oxidative stress created by hydrogen peroxide have not been fully elucidated. SUBJECTS AND METHODS: Oxidative stress was induced by adding hydrogen peroxide at 0.25 mM for 2 hours to rat neonatal cardiomyocytes (rCMCs), rat vascular smooth muscle cells (rVSMCs), and human umbilical vein endothelial cells (HUVECs). Apoptosis was quantified by flow cytometry and the expression patterns of the six PRx isoforms were evaluated by western blotting in the three cell lines after hydrogen peroxide stimulation. Apoptosis and the cell survival signal pathway were evaluated by PRx1 gene delivery using lentiviral vector in hydrogen peroxide stimulated rCMCs versus green fluorescence protein gene delivery. RESULTS: Hydrogen peroxide induced 25% apoptosis in rCMCs. Furthermore, the PRx1 and 5 isoforms were found to be overexpressed in hydrogen peroxide treated rCMCs, and PRx1 overexpression by gene delivery was found to reduce hydrogen peroxide induced rCMCs apoptosis significantly. In addition, this effect was found to originate from cell survival pathway modification. CONCLUSION: Hydrogen peroxide induced significant oxidative stress in rCMCs, rVSMCs, and HUVECs, and PRx1 overexpression using a lentiviral vector system significantly reduced hydrogen peroxide induced rCMCs apoptosis by upregulation of cell survival signals and downregulation of apoptotic signals. These findings suggest that PRx1 could be used as a treatment strategy for myocardial salvage in conditions of oxidative stress.
