Document Detail


H2O2 alters rat cardiac sarcomere function and protein phosphorylation through redox signaling.
MedLine Citation:
PMID:  20562337     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ROS, such as H(2)O(2), are a component of pathological conditions in many organ systems and have been reported to be elevated in cardiac pathophysiology. The experiments presented here test the hypothesis that H(2)O(2) induces alterations in cardiac myofilament function by the posttranslational modification of sarcomeric proteins indirectly through PKC signaling. In vitro assessment of actomyosin Mg(2+)-ATPase activity of myofibrillar fractions showed blunted relative ATP consumption in the relaxed state (pCa 8.0) in response to treatment with 0.5 mM H(2)O(2) before myofilament isolation. The effect was attributable to downstream "redox signaling," inasmuch as the direct application of H(2)O(2) to isolated myofibrils did not alter Mg(2+)-ATPase activity. Ca(2+)-ATPase activity, which was used as a measure of myofibrillar myosin function, was unaffected by H(2)O(2). Functional experiments using rat cardiac trabeculae treated with 0.5 or 5 mM H(2)O(2) followed by detergent extraction of membranes demonstrated increased Ca(2+) sensitivity of force production, a faster rate of force redevelopment, and (for 5 mM) decreased maximum tension. Biochemical analysis of myocardial samples treated with 0.5 mM H(2)O(2) demonstrated increased phosphorylation of two sarcomeric proteins: cardiac troponin I and myosin-binding protein-C. These changes were eliminated by a general PKC inhibitor. However, H(2)O(2) and the general PKC activator PMA induced different phosphorylation patterns in cardiomyocytes in which PKC-delta was elevated by viral infection. These data provide evidence that PKC-dependent redox signaling affects the function of cardiac myofilaments and indicate modification of specific proteins through this signaling mechanism.
Authors:
Benjamin S Avner; Aaron C Hinken; Chao Yuan; 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:  2010-06-18
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  299     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-31     Completed Date:  2010-09-22     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H723-30     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois, Chicago, Illinois 60612-7342, USA.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / drug effects,  metabolism
Analysis of Variance
Animals
Blotting, Western
Ca(2+) Mg(2+)-ATPase / metabolism
Calcium-Transporting ATPases / metabolism
Cells, Cultured
Heart / drug effects
Hydrogen Peroxide / metabolism*,  pharmacology
Male
Myocardial Contraction / drug effects
Myocardium / metabolism
Myocytes, Cardiac / drug effects,  metabolism*
Oxidation-Reduction / drug effects*
Phosphorylation / drug effects*
Rats
Rats, Sprague-Dawley
Sarcomeres / drug effects,  metabolism*
Signal Transduction / drug effects
Grant Support
ID/Acronym/Agency:
P01-HL-062426/HL/NHLBI NIH HHS; R01-HL-22231/HL/NHLBI NIH HHS; T32-007692//PHS HHS
Chemical
Reg. No./Substance:
7722-84-1/Hydrogen Peroxide; EC 3.6.1.-/Ca(2+) Mg(2+)-ATPase; EC 3.6.3.8/Calcium-Transporting ATPases
Comments/Corrections

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