Molecular mechanisms regarding potassium bromate-induced cardiac hypertrophy without apoptosis in H9c2 cells

被引:10
作者
Kuo, Shu-Chun [1 ,2 ]
Li, Yingxiao [3 ,4 ]
Cheng, Yung-Ze [5 ]
Lee, Wei-Jing [5 ]
Cheng, Juei-Tang [3 ,6 ]
Cheng, Kai-Chun [4 ]
机构
[1] Chung Hwa Univ Med Technol, Dept Optometry, Tainan 7170, Taiwan
[2] Chi Mei Med Ctr, Dept Ophthalmol, Tainan 71003, Taiwan
[3] Chi Mei Med Ctr, Dept Med Res, 901 Zhonghua Rd, Tainan 71003, Taiwan
[4] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med, 8-35-1 Sakuragaoka, Kagoshima 890, Japan
[5] Chi Mei Med Ctr, Dept Emergency Med, Tainan 71003, Taiwan
[6] Chang Jung Christian Univ, Grad Sch Med Sci, Tainan 71101, Taiwan
关键词
potassium bromate; oxidative stress; tiron; hypertrophic signals; H9c2; cells; DIABETIC CARDIOMYOPATHY; MYOCYTE APOPTOSIS; OXIDATIVE STRESS; GENE-EXPRESSION; HYPERGLYCEMIA; HEART; PATHWAY; DAMAGE; TIRON; ACID;
D O I
10.3892/mmr.2018.9470
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cardiac hypertrophy is commonly involved in cardiac injury. Oxidative stress can induce cardiac hypertrophy with apoptosis. Potassium bromate (KBrO3) has been widely used as a food additive due to its oxidizing properties. In the present study, the rat-derived heart cell line H9c2 was used to investigate the effect of KBrO3 on cell size. KBrO3 increased cell size at concentrations <250 mu M, in a dose-dependent manner. Additionally, KBrO3 also promoted the gene expression of two biomarkers of cardiac hypertrophy, brain/B-type natriuretic peptides (BNP) and beta-Myosin Heavy Chain (beta-MHC). However, apoptosis remained unobserved in these cells. Moreover, mediation of free radicals was investigated using a fluorescence assay, and it was observed that superoxide and reactive oxygen species (ROS) levels increased with KBrO3. Effects of KBrO3 were significantly reduced by tiron at concentrations sufficient to produce antioxidant-like action. Additionally, signals involved in cardiac hypertrophy such as calcineurin and nuclear factor of activated T-cells (NFAT) were also determined using western blot analysis. KBrO3 increased the protein levels of both these molecules which were decreased by tiron in a dose-dependent manner. Additionally, cyclosporine A attenuated the cardiac hypertrophy induced by KBrO3 in H9c2 cells at concentrations effective to inhibit calcineurin, in addition to reducing mRNA levels of BNP or beta-MHC. Finally, apoptosis was also identified in H9c2 cells incubated with KBrO3 at concentrations >300 mu M. Collectively, these results provided a novel perspective that KBrO3 induces cardiac hypertrophy without apoptosis at a low dose through the generation of ROS, activating the calcineurin/NFAT signaling pathway in H9c2 cells. Therefore, at a dose <250 mu M, KBrO3 can be applied as an inducer of cardiac hypertrophy without apoptosis in H9c2 cells. KBrO3 can also be developed as a tool to induce cardiac hypertrophy in animals.
引用
收藏
页码:4700 / 4708
页数:9
相关论文
共 47 条
[1]  
[Anonymous], J INDIAN ACAD FORENS
[2]   Tropisetron inhibits high glucose-induced calcineurin/NFAT hypertrophic pathway in H9c2 myocardial cells [J].
Asadi, Firouzeh ;
Razmi, Ali ;
Dehpour, Ahmad Reza ;
Shafiei, Massoumeh .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2016, 68 (04) :485-493
[3]   Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies [J].
Bernardo, Bianca C. ;
Weeks, Kate L. ;
Pretorius, Lynette ;
McMullen, Julie R. .
PHARMACOLOGY & THERAPEUTICS, 2010, 128 (01) :191-227
[4]   Down-Modulation of Bcl-2 Sensitizes PTEN-Mutated Prostate Cancer Cells to Starvation and Taxanes [J].
Calastretti, Angela ;
Gatti, Giuliana ;
Quaresmini, Carolina ;
Bevilacqua, Annamaria .
PROSTATE, 2014, 74 (14) :1411-1422
[5]   Characterization of the mechanisms of the increase in PPARδ expression induced by digoxin in the heart using the H9c2 cell line [J].
Chen, Zhih-Cherng ;
Yu, Bu-Chin ;
Chen, Li-Jen ;
Cheng, Kai-Chun ;
Lin, Hung Jung ;
Cheng, Juei-Tang .
BRITISH JOURNAL OF PHARMACOLOGY, 2011, 163 (02) :390-398
[6]   Right ventricular remodelling induced by exercise training in competitive athletes [J].
D'Ascenzi, Flavio ;
Pelliccia, Antonio ;
Corrado, Domenico ;
Cameli, Matteo ;
Curci, Valeria ;
Alvino, Federico ;
Natali, Benedetta Maria ;
Focardi, Marta ;
Bonifazi, Marco ;
Mondillo, Sergio .
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING, 2016, 17 (03) :301-307
[7]   Carcinogenicity of potassium bromate administered in the drinking water to male B6C3F1 mice and F344/N rats [J].
DeAngelo, AB ;
George, MH ;
Kilburn, SR ;
Moore, TM ;
Wolf, DC .
TOXICOLOGIC PATHOLOGY, 1998, 26 (05) :587-594
[8]   Role of histone deacetylase 2 and its posttranslational modifications in cardiac hypertrophy [J].
Eom, Gwang Hyeon ;
Kook, Hyun .
BMB REPORTS, 2015, 48 (03) :131-138
[9]   Interference of antihypertrophic molecules and signaling pathways with the Ca2+-calcineurin-NFAT cascade in cardiac myocytes [J].
Fiedler, B ;
Wollert, KC .
CARDIOVASCULAR RESEARCH, 2004, 63 (03) :450-457
[10]   Cardiac volume overload rapidly induces oxidative stress-mediated myocyte apoptosis and hypertrophy [J].
Fiorillo, C ;
Nediani, C ;
Ponziani, V ;
Giannini, L ;
Celli, A ;
Nassi, N ;
Formigli, L ;
Perna, AM ;
Nassi, P .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2005, 1741 (1-2) :173-182