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    Myocardial Infarction in Mice Alters Sarcomeric Function Via Post-Translational Protein Modification

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    Date
    2012-04
    Author
    Avner, Benjamin S.
    Shioura, Krystyna M.
    Scruggs, Sarah B.
    Geenen, David L.
    Helseth, Donald L. Jr.
    Farjah, Mariam
    Goldspink, Paul H.
    Solaro, R. John
    Publisher
    American Society for Biochemistry and Molecular Biology
    Metadata
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    Abstract
    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.
    Citation
    Avner, B. S. Shioura, K. M. Scruggs, S. B. Grachoff, M. Geenen, D. L. Helseth, D. L., Jr. Farjah, M. Goldspink, P. H. John, Solaro R.. Myocardial infarction in mice alters sarcomeric function via post-translational protein modification. Journal of Biological Chemistry. 2012;363(1-2):203-215. doi: 10.1007/s11010-011-1172-z
    Subject
    myocardial infarction
    reactive oxygen species
    Ca-sensitivity
    ATPase rate
    protein phosphorylation
    Type
    Article
    Date available in INDIGO
    2013-11-22T15:44:45Z
    URI
    http://hdl.handle.net/10027/10591
    Collections
    • Publications - Physiology and Biophysics

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