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Effects of low concentration bisphenol A on calcium spark of female adult rat cardiac myocytes and its mechanism#br# |
YAN Sujuan1 CHENG Xiaoshu2 LI Juxiang2 CHEN Yamei3 DONG Min3 WANG Hongsheng3 |
1.Department of Cardiology, Beijing Electric Power Hospital, Beijing 100073, China;
2.Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Jiangxi Province, Nanchang 330006, China;
3.College of Medicine, University of Cincinnati, State of Ohio, Cincinnati 45267, the United States of America |
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Abstract Objective To investigate the effects and the mechanisms of bisphenol A (BPA) on calcium spark of the female adult rat cardiac myocytes. Methods Twenty healthy female SD rats weighing 200-250 g at 10-16 weeks old were selected and their cardiac myocytes were isolated in vitro after death. According to the experimental requirements, the cells were divided into control group and BPA group (10-9 mmol/L BPA was added). Cells in each group were obtained from at least three rats, and eight to ten cells were taken from each rat. Confocal microscope was used to detect calcium sparks in both groups, and calcium ion imaging system was used to detect calcium transients and calcium load of sarcoplasmic reticulum in two groups. Results Under confocal microscope, bright calcium sparks appeared in both groups. Calcium spark frequency and calcium transient peak value in BPA group were higher than those in control group, while calcium transient tau value was shorter than that in control group, the differences were highly statistically significant (P < 0.01). There was no significant difference between the two groups in calcium spark peak value (P > 0.05). In steady state, the calcium load of sarcoplasmic reticulum in BPA group was higher than that in control group, and the difference was statistically significant (P < 0.05). There was no significant difference in tau value of sarcoplasmic reticulum calcium load between the two groups (P > 0.05). At static state, there was no significant difference in the calcium load of sarcoplasmic reticulum between the two groups (P > 0.05). Conclusion Under the action of BPA, the calcium load in the sarcoplasmic reticulum of female adult rat cardiomyocytes gradually increased with the contraction of cardiomyocytes, and the opening rate of renotin receptor also gradually increased, promoting Ca2+ leakage from the sarcoplasmic reticulum of cardiomyocytes during diastolic period, and increasing the frequency of calcium spark.
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[1] Cheng H,Lederer WJ,Cannell MB. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle [J]. Science,1993,262:740-744.
[2] Shah C,Jiwani S,Limbu B,et al. Delayed afterdepolarization-induced triggered activity in cardiac purkinje cells mediated through cytosolic calcium diffusion waves [J]. Physiol Rep,2019,7(24):e14296.
[3] Staples CA,Dorn PB,Klecka GM,et al. A review of the environmental fate,effects and exposues of bisphenol A [J]. Chemosphere,1998,36(10):2149-2173.
[4] Wazir U,Mokbel K. Bisphenol A:A Concise Review of Literature and a Discussion of Health and Regulatory Implications [J]. In Vivo,2019,33(5):1421-1423.
[5] Radwan M,Wielgomas B,Dziewirska E,et al. Urinary Bisphenol A Levels and Male Fertility [J]. Am J Mens Health,2018,12(6):2144-2215.
[6] Hwang S,Lim JE,Choi Y,et al. Bisphenol A exposure and type 2 diabetes mellitus risk: a meta-analysis [J]. BMC Endocr Disord,2018,18(1):81.
[7] vom Saal FS,Hughes C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment [J]. Environ Health Perspect,2005,113:926-933.
[8] den Braver-Sewradj SP,van Spronsen R,Hessel EVS. Substitution of bisphenol A:a review of the carcinogenicity,reproductive toxicity,and endocrine disruption potential of alternative substances [J]. Crit Rev Toxicol,2020,50(2):128-147.
[9] Calafat AM,Kuklenyik Z,Reidy JA,et al. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population [J]. Environ Health Perspect,2005, 113(4):391-395.
[10] Gaynor JW,Ittenbach RF,Calafat AM,et al. Perioperative Exposure to Suspect Neurotoxicants From Medical Devices in Newborns with Congenital Heart Defects [J]. Ann Thorac Surg,2019,107(2):567-572.
[11] Braun JM. Early-life exposure to EDCs:role in childhood obesity and neurodevelopment [J]. Nat Rev Endocrinol,2017,13:161-173.
[12] Tewar S,Auinger P,Braun JM,et al. Association of bisphenol A exposure and attention-deficit/hyperactivity disorder in a national sample of U.S. children [J]. Environ Res,2016,150:112-118.
[13] Lang IA,Galloway TS,Scarlett A,et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults [J]. JAMA,2008, 300(11):1303-1310.
[14] Amin DM. Role of copeptin as a novel biomarker of bisphenol A toxic effects on cardiac tissues: biochemical,histological,immunohistological,and genotoxic study [J]. Environ Sci Pollut Res Int,2019,26(35):36037-36047.
[15] Zhang YF,Shan C,Wang Y,et al. Cardiovascular toxicity and mechanism of bisphenol A and emerging risk of bisphenol S [J]. Sci Total Environ,2020,723:137952.
[16] Ma J,Hong K,Wang HS. Progesterone Protects Against Bisphenol A-Induced Arrhythmias in Female Rat Cardiac Myocytes via Rapid Signaling [J]. Endocrinology,2017,58(4):778-790.
[17] Belcher SM,Chen Y,Yan S,et al. Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17β-estradiol and the environmental endocrine disruptor bisphenol A [J]. Endocrinology,2012,153(2):712-720.
[18] Cranefield PF. The conduction of the cardiac impulse [M]. New York:Future Press,Mount Kisco,1975.
[19] Kistamás K,Veress R,Horváth B,et al. Calcium Handling Defects and Cardiac Arrhythmia Syndromes [J]. Front Pharmacol,2020,11:72.
[20] Fill M,Mejía-Alvarez R,Kettlun C,et al. Ryanodine receptor permeation and gating:glowing cinders that underlie the Ca2+ spark [J]. J Gen Physiol,1999,114(1):159-161.
[21] Guo T,Zhang T,Mestril R,et al. Ca2+/Calmodulin-dependent protein kinase Ⅱ phosphorylation of ryanodine receptor does affect calcium sparks in mouse ventricular myocytes [J]. Circ Res,2006,99(4):398-406.
[22] Wehrens XH,Lehnart SE,Marks AR. Intracellular calcium release and cardiac disease [J]. Annu Rev Physiol,2005,67:69-98.
[23] Zhu W,Wang C,Hu J. Circulation Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor [J]. Hyperphosphorylation,2018,138(23):2682-2697.
[24] Lehnart SE,Mongillo M,Bellinger A,et al. Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice [J]. J Clin Invest,2008, 118(6):2230-2245.
[25] Kohno M,Yano M,Kobayashi S,et al. A new cardioprotective agent,JTV519,improves defective channel gating of ryanodine receptor in heart failure [J]. Am J Physiol Heart Circ Physiol,2003,284(3):H1035-H1042.
[26] Yano M,Kobayashi S,Kohno M,et al. FKBP12.6-mediated stabilization of calcium-release channel(ryanodine receptor)as a novel therapeutic strategy against heart failure [J]. Circulation,2003,107(3):477-484. |
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