| Reduced force production during low blood flow to the heart correlates with altered troponin I phosphorylation. | |
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MedLine Citation:
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PMID: 19507043 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A rat model of low myocardial blood flow was established to test the hypothesis that post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following 3 days of low blood flow by constriction of the left anterior descending artery, rat hearts demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose versus low dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force per cross-section and Ca2+ sensitivity as compared to their sham operated counterparts. An examination of sarcomeric proteins by twodimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies provided evidence for Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in phosphorylation at other sites of TnI. Affinity chromatography demonstrated that TnI from low blood flow myocardium had reduced relative affinity to Ca2+ bound troponin C compared to TnI from sham operated hearts, providing a mechanism for reduced Ca2+ sensitivity of force production in low blood flow fibers. These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart. |
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Authors:
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Bridgette Christopher; Gresin O Pizarro; Bryson Nicholson; Samantha Yuen; Brian D Hoit; Ozgur Ogut |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-06-09 |
Journal Detail:
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Title: Journal of muscle research and cell motility Volume: 30 ISSN: 1573-2657 ISO Abbreviation: J. Muscle Res. Cell. Motil. Publication Date: 2009 |
Date Detail:
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Created Date: 2009-08-28 Completed Date: 2009-11-02 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8006298 Medline TA: J Muscle Res Cell Motil Country: Netherlands |
Other Details:
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Languages: eng Pagination: 111-23 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Flow Velocity Calcium / metabolism* Cardiac Myosins / metabolism Dobutamine / pharmacology Heart / drug effects, physiology* Microfilaments / metabolism* Myocardial Contraction / drug effects, physiology* Myosin Light Chains / metabolism Phosphorylation Rats Troponin C / metabolism Troponin I / metabolism* Troponin T / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL078845/HL/NHLBI NIH HHS; R01 HL078845-04/HL/NHLBI NIH HHS; T32 GM07250/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Myosin Light Chains; 0/Troponin C; 0/Troponin I; 0/Troponin T; 0/myosin light chain 2; 34368-04-2/Dobutamine; 7440-70-2/Calcium; EC 3.6.1.-/Cardiac Myosins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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