Journal article
Myocardial infarction in mice alters sarcomeric function via post-translational protein modification
Molecular and cellular biochemistry, Vol.363(1-2), pp.203-215
04/01/2012
DOI: 10.1007/s11010-011-1172-z
PMCID: PMC3659404
PMID: 22160857
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. Ca2+ 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 Ca2+ 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.
Details
- Title: Subtitle
- Myocardial infarction in mice alters sarcomeric function via post-translational protein modification
- Creators
- Benjamin S. Avner - University of Illinois ChicagoKrystyna M. Shioura - University of Illinois ChicagoSarah B. Scruggs - University of California, Los AngelesMilana Grachoff - University of Illinois ChicagoDavid L. Geenen - University of Illinois ChicagoDonald L. Helseth - University of Illinois ChicagoMariam Farjah - University of Illinois ChicagoPaul H. Goldspink - University of Illinois ChicagoR. John Solaro - University of Illinois Chicago
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biochemistry, Vol.363(1-2), pp.203-215
- DOI
- 10.1007/s11010-011-1172-z
- PMID
- 22160857
- PMCID
- PMC3659404
- NLM abbreviation
- Mol Cell Biochem
- ISSN
- 0300-8177
- eISSN
- 1573-4919
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- 2008-06682-00-00 / American Heart Association T32 007692; PO1 HL062426 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 04/01/2012
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985237504002771
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