| Overexpression of SERCA1a in the mdx diaphragm reduces susceptibility to contraction-induced damage. | |
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MedLine Citation:
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PMID: 20540606 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the precise pathophysiological mechanism of muscle damage in dystrophin-deficient muscle remains disputed, calcium appears to be a critical mediator of the dystrophic process. Duchenne muscular dystrophy patients and mouse models of dystrophin deficiency exhibit extensive abnormalities of calcium homeostasis, which we hypothesized would be mitigated by increased expression of the sarcoplasmic reticulum calcium pump. Neonatal adeno-associated virus gene transfer of sarcoplasmic reticulum ATPase 1a to the mdx diaphragm decreased centrally located nuclei and resulted in reduced susceptibility to eccentric contraction-induced damage at 6 months of age. As the diaphragm is the mouse muscle most representative of human disease, these results provide impetus for further investigation of therapeutic strategies aimed at enhanced cytosolic calcium removal. |
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Authors:
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Kevin J Morine; Meg M Sleeper; Elisabeth R Barton; H Lee Sweeney |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Human gene therapy Volume: 21 ISSN: 1557-7422 ISO Abbreviation: Hum. Gene Ther. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-06-29 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1735-9 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA. kmorine@gmail.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Dependovirus / genetics Diaphragm / metabolism*, physiopathology Gene Therapy Gene Transfer Techniques Genetic Vectors Humans Mice Mice, Inbred C57BL Mice, Inbred mdx Muscle Contraction* Muscle Strength Protein Isoforms / biosynthesis Recombinant Proteins / biosynthesis* Sarcoplasmic Reticulum Calcium-Transporting ATPases / biosynthesis* Transgenes |
| Grant Support | |
ID/Acronym/Agency:
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U54-AR052646/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protein Isoforms; 0/Recombinant Proteins; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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