| Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. | |
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MedLine Citation:
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PMID: 11517337 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiac muscle regeneration after injury is limited by "irreversible" cell cycle exit. Telomere shortening is one postulated basis for replicative senescence, via down-regulation of telomerase reverse transcriptase (TERT); telomere dysfunction also is associated with greater sensitivity to apoptosis. Forced expression of TERT in cardiac muscle in mice was sufficient to rescue telomerase activity and telomere length. Initially, the ventricle was hypercellular, with increased myocyte density and DNA synthesis. By 12 wk, cell cycling subsided; instead, cell enlargement (hypertrophy) was seen, without fibrosis or impaired function. Likewise, viral delivery of TERT was sufficient for hypertrophy in cultured cardiac myocytes. The TERT virus and transgene also conferred protection from apoptosis, in vitro and in vivo. Hyperplasia, hypertrophy, and survival all required active TERT and were not seen with a catalytically inactive mutation. Thus, TERT can delay cell cycle exit in cardiac muscle, induce hypertrophy in postmitotic cells, and promote cardiac myocyte survival. |
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Authors:
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H Oh; G E Taffet; K A Youker; M L Entman; P A Overbeek; L H Michael; M D Schneider |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2001-08-21 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 98 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-08-29 Completed Date: 2001-10-04 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 10308-13 Citation Subset: IM; S |
Affiliation:
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Center for Cardiovascular Development, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology Base Sequence Cardiomegaly / enzymology, etiology Cell Division / physiology Cell Size / physiology Cell Survival / physiology Cells, Cultured DNA Primers / genetics DNA-Binding Proteins Gene Expression Regulation, Developmental Humans Mice Mice, Transgenic Myocardium / cytology*, enzymology* Rats Telomerase / genetics, physiology* Telomere / ultrastructure |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/DNA-Binding Proteins; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse |
| Comments/Corrections | |
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