| Myocardial infarction in mice alters sarcomeric function via post-translational protein modification. | |
MedLine Citation:
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PMID: 22160857 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myocardial physiology in the aftermath of myocardial infarction (MI) before remodeling is an under-explored area of investigation. Here, we describe the effects of MI on the cardiac sarcomere with focus on the possible contributions of reactive oxygen species. We surgically induced MI in 6-7-month-old female CD1 mice by ligation of the left anterior descending coronary artery. Data were collected 3-4 days after MI or sham (SH) surgery. MI hearts demonstrated ventricular dilatation and systolic dysfunction upon echo cardiographic analysis. Sub-maximum Ca-activated tension in detergent-extracted fiber bundles from papillary muscles increased significantly in the preparations from MI hearts. Ca(2+) sensitivity increased after MI, whereas cooperativity of activation decreased. To assess myosin enzymatic integrity we measured splitting of Ca-ATP in myofibrillar preparations, which demonstrated a decline in Ca-ATPase activity of myofilament myosin. Biochemical analysis demonstrated post-translational modification of sarcomeric proteins. Phosphorylation of cardiac troponin I and myosin light chain 2 was reduced after MI in papillary samples, as measured using a phospho-specific stain. Tropomyosin was oxidized after MI, forming disulfide products detectable by diagonal non-reducing-reducing SDS-PAGE. Our analysis of myocardial protein oxidation post-MI also demonstrated increased S-glutathionylation. We functionally linked protein oxidation with sarcomere function by treating skinned fibers with the sulfhydryl reducing agent dithiothreitol, which reduced Ca(2+) sensitivity in MI, but not SH, samples. Our data indicate important structural and functional alterations to the cardiac sarcomere after MI, and the contribution of protein oxidation to this process. |
Authors:
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Benjamin S Avner; Krystyna M Shioura; Sarah B Scruggs; Milana Grachoff; David L Geenen; Donald L Helseth; Mariam Farjah; Paul H Goldspink; R John Solaro |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-12-08 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 363 ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-02-29 Completed Date: 2012-07-02 Revised Date: 2013-06-27 |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 203-15 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics, (M/C 901), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612-7342, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Calcium / metabolism Calcium-Transporting ATPases / metabolism Cardiac Myosins / metabolism Disease Models, Animal Dithiothreitol / pharmacology Electrophoresis, Polyacrylamide Gel Female Glutathione / metabolism Mice Molecular Sequence Data Muscle Proteins / metabolism* Myocardial Contraction* Myocardial Infarction / metabolism*, physiopathology, ultrasonography Myosin Light Chains / metabolism Oxidation-Reduction Papillary Muscles / drug effects, metabolism*, physiopathology Phosphorylation Protein Processing, Post-Translational* Reactive Oxygen Species / metabolism Reducing Agents / pharmacology Sarcomeres / drug effects, metabolism* Stroke Volume Tropomyosin / metabolism Troponin I / metabolism Ventricular Function, Left* |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL062426/HL/NHLBI NIH HHS; P01 HL062426/HL/NHLBI NIH HHS; T32 007692//PHS HHS; T32 HL007692/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Muscle Proteins; 0/Myosin Light Chains; 0/Reactive Oxygen Species; 0/Reducing Agents; 0/Tropomyosin; 0/Troponin I; 0/myosin light chain 2; 3483-12-3/Dithiothreitol; 70-18-8/Glutathione; 7440-70-2/Calcium; EC 3.6.1.-/Cardiac Myosins; EC 3.6.3.8/Calcium-Transporting ATPases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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