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Matrine alleviates AGEs- induced cardiac dysfunctions by attenuating calcium overload via reducing ryanodine receptor 2 activity.
Eur J Pharmacol. 2019 Jan 05; 842:118-124.EJ

Abstract

Featured by heart dysfunction, the diabetic cardiomyopathy is causing mortality and morbidity in type 2 diabetes mellitus patients. Matrine was considered as a cardioprotective agent. This study was aimed to investigate the therapeutic effects and molecular mechanisms of matrine on advanced glycation end products (AGEs)- induced cardiac dysfunctions. Rats and isolated primary myocytes were exposed to AGEs. Left ventricular hemodynamic parameters were used to assess the cardiac function. Cell apoptosis was detected with TUNEL assay. Calcium indicator was used to determine the intracellular calcium concentration ([Ca2+]i). The molecular coupling between FK506-binding protein 12.6 (FKBP12.6) and ryanodine receptor 2 (RyR2) was evaluated by immunoprecipitation. Apoptotic protein expressions were measured by western blotting. The activity of RyR2 was measured by [3H]-ryanodine binding assay. AGEs exposure impaired systolic and diastolic functions and induced apoptosis in myocardium. AGEs exposure also elevated [Ca2+]i, decreased mitochondrial membrane potential (MMP) and induced cell apoptosis in myocardium and cultured myocytes. AGEs impaired association between FKBP12.6 and RyR2 and further increased RyR2 activity in vivo and in vitro. The expression levels of cytochrome c and active caspase3 were elevated by AGEs exposure. Matrine treatment improved cardiac function in AGEs- exposed hearts. Matrine inhibited the disassociation of FKBP12.6 and RyR2, decreased the activity of RyR2, [Ca2+]i, apoptosis, expression levels of cytochrome c and active caspase3 in vivo and in vitro. Matrine attenuated AGEs- induced cardiac dysfunctions by regulating RyR2- mediated calcium overload- triggered myocardial apoptosis.

Authors+Show Affiliations

Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China.Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China.Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China.Department of Biostatistics & Bioinformatics, School of Public Health & Tropical Medicine, Tulane University, 70112 New Orleans, LA, USA.Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China.Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China.Department of Cardiology, Shaanxi Provincial People's Hospital, Medical Research Institute of Northwestern Polytechnical University, 710068 Xi'an, China. Electronic address: liuzhongwei@xjtu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30339815

Citation

Wang, Junkui, et al. "Matrine Alleviates AGEs- Induced Cardiac Dysfunctions By Attenuating Calcium Overload Via Reducing Ryanodine Receptor 2 Activity." European Journal of Pharmacology, vol. 842, 2019, pp. 118-124.
Wang J, Tang Z, Zhang Y, et al. Matrine alleviates AGEs- induced cardiac dysfunctions by attenuating calcium overload via reducing ryanodine receptor 2 activity. Eur J Pharmacol. 2019;842:118-124.
Wang, J., Tang, Z., Zhang, Y., Qiu, C., Zhu, L., Zhao, N., & Liu, Z. (2019). Matrine alleviates AGEs- induced cardiac dysfunctions by attenuating calcium overload via reducing ryanodine receptor 2 activity. European Journal of Pharmacology, 842, 118-124. https://doi.org/10.1016/j.ejphar.2018.10.010
Wang J, et al. Matrine Alleviates AGEs- Induced Cardiac Dysfunctions By Attenuating Calcium Overload Via Reducing Ryanodine Receptor 2 Activity. Eur J Pharmacol. 2019 Jan 5;842:118-124. PubMed PMID: 30339815.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrine alleviates AGEs- induced cardiac dysfunctions by attenuating calcium overload via reducing ryanodine receptor 2 activity. AU - Wang,Junkui, AU - Tang,Zhiguo, AU - Zhang,Yong, AU - Qiu,Chuan, AU - Zhu,Ling, AU - Zhao,Na, AU - Liu,Zhongwei, Y1 - 2018/10/16/ PY - 2018/07/06/received PY - 2018/10/01/revised PY - 2018/10/10/accepted PY - 2018/10/20/pubmed PY - 2019/2/26/medline PY - 2018/10/20/entrez KW - AGEs KW - Apoptosis KW - Calcium KW - Matrine KW - RyR2 SP - 118 EP - 124 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 842 N2 - Featured by heart dysfunction, the diabetic cardiomyopathy is causing mortality and morbidity in type 2 diabetes mellitus patients. Matrine was considered as a cardioprotective agent. This study was aimed to investigate the therapeutic effects and molecular mechanisms of matrine on advanced glycation end products (AGEs)- induced cardiac dysfunctions. Rats and isolated primary myocytes were exposed to AGEs. Left ventricular hemodynamic parameters were used to assess the cardiac function. Cell apoptosis was detected with TUNEL assay. Calcium indicator was used to determine the intracellular calcium concentration ([Ca2+]i). The molecular coupling between FK506-binding protein 12.6 (FKBP12.6) and ryanodine receptor 2 (RyR2) was evaluated by immunoprecipitation. Apoptotic protein expressions were measured by western blotting. The activity of RyR2 was measured by [3H]-ryanodine binding assay. AGEs exposure impaired systolic and diastolic functions and induced apoptosis in myocardium. AGEs exposure also elevated [Ca2+]i, decreased mitochondrial membrane potential (MMP) and induced cell apoptosis in myocardium and cultured myocytes. AGEs impaired association between FKBP12.6 and RyR2 and further increased RyR2 activity in vivo and in vitro. The expression levels of cytochrome c and active caspase3 were elevated by AGEs exposure. Matrine treatment improved cardiac function in AGEs- exposed hearts. Matrine inhibited the disassociation of FKBP12.6 and RyR2, decreased the activity of RyR2, [Ca2+]i, apoptosis, expression levels of cytochrome c and active caspase3 in vivo and in vitro. Matrine attenuated AGEs- induced cardiac dysfunctions by regulating RyR2- mediated calcium overload- triggered myocardial apoptosis. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/30339815/Matrine_alleviates_AGEs__induced_cardiac_dysfunctions_by_attenuating_calcium_overload_via_reducing_ryanodine_receptor_2_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(18)30585-5 DB - PRIME DP - Unbound Medicine ER -