| Reduced expression of the Na+/Ca2+ exchanger in adult cardiomyocytes via adenovirally delivered shRNA results in resistance to simulated ischemic injury. | |
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MedLine Citation:
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PMID: 19966047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Na(+)/Ca(2+) exchanger (NCX) is proposed to be an important protein in the regulation of Ca(2+) movements in the heart. This Ca(2+) regulatory action is thought to modulate contractile activity in the heart under normal physiological conditions and may contribute to the Ca(2+) overload that occurs during ischemic reperfusion challenge. To evaluate these hypotheses, adult rat cardiomyocytes were exposed to an adenovirus that codes for short hairpin RNA (shRNA) targeting NCX gene expression through RNA interference. An adenovirus transcribing a short RNA with a scrambled nucleotide sequence was compared with the NCX-shRNA nucleotide sequence and used as a control. Freshly isolated rat cardiomyocytes were infected with virus for 48 h before examination. Cardiomyocytes maintained their characteristic morphological appearance during this short time period after isolation. NCX expression was inhibited by up to approximately 60% by the shRNA treatment as determined by Western blot analysis. The depletion in NCX protein was accompanied by a significant depression of NCX activity in shRNA-treated cells. Ca(2+) homeostasis was unaltered in the shRNA-treated cells upon electrical stimulation compared with control cells. However, when cardiomyocytes were exposed to a simulated ischemic solution, NCX-depleted cells were significantly protected from the rise in cytoplasmic Ca(2+) and damage that was detected in control cells during ischemia and reperfusion. Our data support the role for NCX in ischemic injury to the heart and demonstrate the usefulness of altering gene expression with an adenoviral-delivery system of shRNA in adult cardiomyocytes. |
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Authors:
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Thane G Maddaford; Elena Dibrov; Cecilia Hurtado; Grant N Pierce |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-04 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 298 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-02-16 Revised Date: - |
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: H360-6 Citation Subset: IM |
Affiliation:
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Department of Physiology, St. Boniface Hospital Research Centre, 351 Tache Ave., Winnipeg, MB, Canada R2H 2A6. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics* Animals Calcium / metabolism Cells, Cultured Disease Models, Animal Gene Expression Regulation / drug effects Homeostasis / physiology Myocardial Contraction / physiology Myocardial Reperfusion Injury / metabolism, physiopathology, prevention & control* Myocytes, Cardiac / cytology, drug effects*, metabolism* RNA / genetics, pharmacology* Rats Rats, Sprague-Dawley Sodium-Calcium Exchanger / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Sodium-Calcium Exchanger; 63231-63-0/RNA; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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