Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

被引：16
作者：
Cheng, Wen-Pin [1 ]
Lo, Huey-Ming [2 ,3 ]
Wang, Bao-Wei [1 ]
Chua, Su-Kiat [2 ,4 ,5 ]
Lu, Ming-Jen [6 ]
Shyu, Kou-Gi [2 ]
机构：
[1] Shin Kong Wu Ho Su Mem Hosp, Dept Med Educ & Res, Taipei, Taiwan
[2] Shin Kong Wu Ho Su Mem Hosp, Div Cardiol, 95 Wen Chang Rd, Taipei 111, Taiwan
[3] Fu Jen Catholic Univ, Sch Med, New Taipei, Taiwan
[4] Taipei Med Univ, Grad Inst Clin Med, Coll Med, Taipei, Taiwan
[5] Shin Kong Wu Ho Su Mem Hosp, Dept Gen Med, Taipei, Taiwan
[6] Shin Kong Wu Ho Su Mem Hosp, Div Cardiovas Surg, Dept Surg, Taipei, Taiwan
来源：
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION | 2017年 / 116卷 / 05期
关键词：
AMI; atorvastatin; cardiomyocytes; hypoxia; TRB3; OXIDATIVE STRESS; PROTECTS CARDIOMYOCYTES; CELLS; EXPRESSION; HEART; PALMITATE; PATHWAY; MODEL; BETA;
D O I：
10.1016/j.jfma.2016.07.010
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background/Purpose: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. Methods: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O-2 to induce hypoxia. Results: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-alpha (TNF-alpha) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-alpha antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-alpha from cardiomyocytes. Exogenous administration of TNF-alpha recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-alpha antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-alpha, JNK, and the GADD153 pathway. Conclusion: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia. Copyright (C) 2016, Formosan Medical Association. Published by Elsevier Taiwan LLC.
引用
收藏
页码：388 / 397
页数：10
相关论文
共 36 条
[1]   Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress [J].
Abdel-Hamid, Ahmed A. M. ;
Firgany, Alaa El-Din L. .
JOURNAL OF MOLECULAR HISTOLOGY, 2015, 46 (4-5) :337-345
[2]   TRB3 Function in Cardiac Endoplasmic Reticulum Stress [J].
Avery, Joan ;
Etzion, Sharon ;
DeBosch, Brian J. ;
Jin, Xiaohua ;
Lupu, Traian S. ;
Beitinjaneh, Bassel ;
Grand, Jacob ;
Kovacs, Attila ;
Sambandam, Nandakumar ;
Muslin, Anthony J. .
CIRCULATION RESEARCH, 2010, 106 (09) :1516-U160
[3]   UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression [J].
Bromati, Carla R. ;
Lellis-Santos, Camilo ;
Yamanaka, Tatiana S. ;
Nogueira, Tatiane C. A. ;
Leonelli, Mauro ;
Caperuto, Luciana C. ;
Gorjao, Renata ;
Leite, Adriana R. ;
Anhe, Gabriel F. ;
Bordin, Silvana .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2011, 300 (01) :R92-R100
[4]   TNF-α-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs [J].
Chen, Zhang-Wei ;
Qian, Ju-Ying ;
Ma, Jian-Ying ;
Chang, Shu-Fu ;
Yun, Hong ;
Jin, Hang ;
Sun, Ai-Jun ;
Zou, Yun-Zeng ;
Ge, Jun-Bo .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2014, 18 (10) :1953-1963
[5]   Mechanical Stretch Induces Apoptosis Regulator TRB3 in Cultured Cardiomyocytes and Volume-Overloaded Heart [J].
Cheng, Wen-Pin ;
Wang, Bao-Wei ;
Lo, Huey-Ming ;
Shyu, Kou-Gi .
PLOS ONE, 2015, 10 (04)
[6]   Atorvastatin treatment improves effects of implanted mesenchymal stem cells: meta-analysis of animal models with acute myocardial infarction [J].
Dai, Guo ;
Xu, Qing ;
Luo, Rong ;
Gao, Jianfang ;
Chen, Hui ;
Deng, Yun ;
Li, Yongqing ;
Wang, Yuequn ;
Yuan, Wuzhou ;
Wu, Xiushan .
BMC CARDIOVASCULAR DISORDERS, 2015, 15
[7]   Hrd1 and ER-Associated Protein Degradation, ERAD, Are Critical Elements of the Adaptive ER Stress Response in Cardiac Myocytes [J].
Doroudgar, Shirin ;
Voelkers, Mirko ;
Thuerauf, Donna J. ;
Khan, Mohsin ;
Mohsin, Sadia ;
Respress, Jonathan L. ;
Wang, Wei ;
Gude, Natalie ;
Mueller, Oliver J. ;
Wehrens, Xander H. T. ;
Sussman, Mark A. ;
Glembotski, Christopher C. .
CIRCULATION RESEARCH, 2015, 117 (06) :536-546
[8]   Brief Report: Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure [J].
Hashem, Sherin I. ;
Perry, Cynthia N. ;
Bauer, Matthieu ;
Han, Sangyoon ;
Clegg, Stacey D. ;
Ouyang, Kunfu ;
Deacon, Dekker C. ;
Spinharney, Mary ;
Panopoulos, Athanasia D. ;
Belmonte, Juan Carlos Izpisua ;
Frazer, Kelly A. ;
Chen, Ju ;
Gong, Qiuming ;
Zhou, Zhengfeng ;
Chi, Neil C. ;
Adler, Eric D. .
STEM CELLS, 2015, 33 (07) :2343-2350
[9]   Loss of TRB3 Alters Dynamics of MLK3-JNK Signaling and Inhibits Cytokine-activated Pancreatic Beta Cell Death [J].
Humphrey, Rohan K. ;
Ray, Anamika ;
Gonuguntla, Sumati ;
Hao, Ergeng ;
Jhala, Ulupi S. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (43) :29994-30004
[10]   TanshinoneIIA and Cryptotanshinone Protect against Hypoxia-Induced Mitochondrial Apoptosis in H9c2 Cells [J].
Jin, Hyou-Ju ;
Xie, Xiao-Liang ;
Ye, Ji-Ming ;
Li, Chun-Guang .
PLOS ONE, 2013, 8 (01)
1234