Document Detail

Myocardial infarction in mice alters sarcomeric function via post-translational protein modification.
MedLine Citation:
PMID:  22160857     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-08
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  363     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-07-02     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  203-15     Citation Subset:  IM    
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.
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MeSH Terms
Amino Acid Sequence
Calcium / metabolism
Calcium-Transporting ATPases / metabolism
Cardiac Myosins / metabolism
Disease Models, Animal
Dithiothreitol / pharmacology
Electrophoresis, Polyacrylamide Gel
Glutathione / metabolism
Molecular Sequence Data
Muscle Proteins / metabolism*
Myocardial Contraction*
Myocardial Infarction / metabolism*,  physiopathology,  ultrasonography
Myosin Light Chains / metabolism
Papillary Muscles / drug effects,  metabolism*,  physiopathology
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
P01 HL062426/HL/NHLBI NIH HHS; P01 HL062426/HL/NHLBI NIH HHS; T32 007692//PHS HHS; T32 HL007692/HL/NHLBI NIH HHS
Reg. No./Substance:
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 ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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