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Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients

BACKGROUND: Leonurus heterophyllus sweet has been suggested to have cardioprotective effects against heart diseases, including ischemic diseases and ventricular remodeling. However, the active ingredients of the herb and the underlying mechanisms are poorly understood. The aim of the present study w...

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Autores principales: Zhang, Chen, Shan, Xiao-Li, Liao, Yue-Ling, Zhao, Pei, Guo, Wei, Wei, Hong-Chang, Lu, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295334/
https://www.ncbi.nlm.nih.gov/pubmed/25488774
http://dx.doi.org/10.1186/1472-6882-14-474
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author Zhang, Chen
Shan, Xiao-Li
Liao, Yue-Ling
Zhao, Pei
Guo, Wei
Wei, Hong-Chang
Lu, Rong
author_facet Zhang, Chen
Shan, Xiao-Li
Liao, Yue-Ling
Zhao, Pei
Guo, Wei
Wei, Hong-Chang
Lu, Rong
author_sort Zhang, Chen
collection PubMed
description BACKGROUND: Leonurus heterophyllus sweet has been suggested to have cardioprotective effects against heart diseases, including ischemic diseases and ventricular remodeling. However, the active ingredients of the herb and the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of stachydrine (STA), a major constituent of Leonurus heterophyllus sweet, on norepinephrine (NE) induced hypertrophy and the changes of calcium transients in neonatal rat cardiomyocytes. METHODS: Ventricular myocytes from 1-day-old Wistar rats were isolated and cultured in DMEM/F12 with 1 μmol/L norepinephrine in the presence or absence of 10 μmol/L STA for 72 h. Cardiomyocytes hypertrophy was evaluated by cell surface area, total protein/DNA content, β/α-MHC mRNA ratio. While calcium handling function was evaluated by Ca(2+)-transient amplitude and decay, SERCA2a activity and expression, PLN expression and phosphorylation. β1-adrenergic receptor system activation was evaluated by the content of cAMP and the activation of PKA. RESULTS: NE treatment increases the cell surface area, protein synthesis, the expression level of β-MHC and β/α-MHC ratio. These effects were attenuated by STA. NE-induced hypertrophy was associated with increased Ca(2+)-transient amplitude, accelerated decay of the Ca(2+)-transient, increased phospholamban expression, hyper-phosphorylation at both the serine-16 and threonine-17 residues, increased intracellular cAMP level, and PKA overactivation. All of which were significantly inhibited by STA. CONCLUSION: These data suggest that STA attenuates norepinephrine-induced cardiomyocyte hypertrophy and has potential protective effects against β-adrenergic receptor induced Ca(2+) mishandling.
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spelling pubmed-42953342015-01-16 Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients Zhang, Chen Shan, Xiao-Li Liao, Yue-Ling Zhao, Pei Guo, Wei Wei, Hong-Chang Lu, Rong BMC Complement Altern Med Research Article BACKGROUND: Leonurus heterophyllus sweet has been suggested to have cardioprotective effects against heart diseases, including ischemic diseases and ventricular remodeling. However, the active ingredients of the herb and the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of stachydrine (STA), a major constituent of Leonurus heterophyllus sweet, on norepinephrine (NE) induced hypertrophy and the changes of calcium transients in neonatal rat cardiomyocytes. METHODS: Ventricular myocytes from 1-day-old Wistar rats were isolated and cultured in DMEM/F12 with 1 μmol/L norepinephrine in the presence or absence of 10 μmol/L STA for 72 h. Cardiomyocytes hypertrophy was evaluated by cell surface area, total protein/DNA content, β/α-MHC mRNA ratio. While calcium handling function was evaluated by Ca(2+)-transient amplitude and decay, SERCA2a activity and expression, PLN expression and phosphorylation. β1-adrenergic receptor system activation was evaluated by the content of cAMP and the activation of PKA. RESULTS: NE treatment increases the cell surface area, protein synthesis, the expression level of β-MHC and β/α-MHC ratio. These effects were attenuated by STA. NE-induced hypertrophy was associated with increased Ca(2+)-transient amplitude, accelerated decay of the Ca(2+)-transient, increased phospholamban expression, hyper-phosphorylation at both the serine-16 and threonine-17 residues, increased intracellular cAMP level, and PKA overactivation. All of which were significantly inhibited by STA. CONCLUSION: These data suggest that STA attenuates norepinephrine-induced cardiomyocyte hypertrophy and has potential protective effects against β-adrenergic receptor induced Ca(2+) mishandling. BioMed Central 2014-12-08 /pmc/articles/PMC4295334/ /pubmed/25488774 http://dx.doi.org/10.1186/1472-6882-14-474 Text en © Zhang et al.; licensee BioMed Central. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Chen
Shan, Xiao-Li
Liao, Yue-Ling
Zhao, Pei
Guo, Wei
Wei, Hong-Chang
Lu, Rong
Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title_full Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title_fullStr Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title_full_unstemmed Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title_short Effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
title_sort effects of stachydrine on norepinephrine-induced neonatal rat cardiac myocytes hypertrophy and intracellular calcium transients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295334/
https://www.ncbi.nlm.nih.gov/pubmed/25488774
http://dx.doi.org/10.1186/1472-6882-14-474
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