| {beta}1-Adrenergic receptor activation induces mouse cardiac myocyte death through both L-type calcium channel-dependent and -independent pathways. | |
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MedLine Citation:
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PMID: 20495143 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac diseases persistently increase the contractility demands of cardiac myocytes, which require activation of the sympathetic nervous system and subsequent increases in myocyte Ca(2+) transients. Persistent exposure to sympathetic and/or Ca(2+) stress is associated with myocyte death. This study examined the respective roles of persistent beta-adrenergic receptor (beta-AR) agonist exposure and high Ca(2+) concentration in myocyte death. Ventricular myocytes (VMs) were isolated from transgenic (TG) mice with cardiac-specific and inducible expression of the beta(2a)-subunit of the L-type Ca(2+) channel (LTCC). VMs were cultured, and the rate of myocyte death was measured in the presence of isoproterenol (ISO), other modulators of Ca(2+) handling and the beta-adrenergic system, and inhibitors of caspases and reactive oxygen species generation. The rate of myocyte death was greater in TG vs. wild-type myocytes and accelerated by ISO in both groups, although ISO did not increase LTCC current (I(Ca-L)) in TG-VMs. Nifedipine, an LTCC antagonist, only partially prevented myocyte death. These results suggest both LTCC-dependent and -independent mechanisms in ISO induced myocyte death. ISO increased the contractility of wild type and TG-VMs by enhancing sarcoplasmic reticulum function and inhibiting sarco(endo)plasmic reticulum Ca(2+)-ATPase, Na(+)/Ca(2+) exchanger, and CaMKII partially protected myocyte from death induced by both Ca(2+) and ISO. Caspase and reactive oxygen species inhibitors did not, but beta(2)-AR activation did, reduce myocyte death induced by enhanced I(Ca-L) and ISO stimulation. Our results suggest that catecholamines induce myocyte necrosis primarily through beta(1)-AR-mediated increases in I(Ca-L), but other mechanisms are also involved in rodents. |
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Authors:
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Wei Wang; Hongyu Zhang; Hui Gao; Hajime Kubo; Remus M Berretta; Xiongwen Chen; Steven R Houser |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-05-21 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H322-31 Citation Subset: IM |
Affiliation:
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Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-1 Receptor Agonists* Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists / pharmacology* Animals Antioxidants / pharmacology Calcium Channel Blockers / pharmacology Calcium Channels, L-Type / drug effects*, genetics, metabolism Calcium Signaling / drug effects* Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors, metabolism Caspases / antagonists & inhibitors, metabolism Cell Survival / drug effects Cells, Cultured Cysteine Proteinase Inhibitors / pharmacology Isoproterenol / pharmacology* Membrane Potentials Mice Mice, Transgenic Myocardial Contraction / drug effects* Myocytes, Cardiac / drug effects*, metabolism, pathology Necrosis Protein Subunits Reactive Oxygen Species / metabolism Receptors, Adrenergic, beta-1 / metabolism Receptors, Adrenergic, beta-2 / metabolism Sarcoplasmic Reticulum / drug effects, metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors, metabolism Sodium-Calcium Exchanger / antagonists & inhibitors*, metabolism Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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HL033921/HL/NHLBI NIH HHS; HL088243/HL/NHLBI NIH HHS; HL089312/HL/NHLBI NIH HHS; HL091799/HL/NHLBI NIH HHS; R01 HL088243-01/HL/NHLBI NIH HHS; R01 HL088243-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrb1 protein, mouse; 0/Adrenergic beta-1 Receptor Agonists; 0/Adrenergic beta-2 Receptor Agonists; 0/Adrenergic beta-Agonists; 0/Antioxidants; 0/Calcium Channel Blockers; 0/Calcium Channels, L-Type; 0/Cysteine Proteinase Inhibitors; 0/Protein Subunits; 0/Reactive Oxygen Species; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 0/Sodium-Calcium Exchanger; 7683-59-2/Isoproterenol; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 3.4.22.-/Caspases; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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