The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy.

Cardiovascular Research
Adam JacquesSteven B Marston

Abstract

The aim of the study was to compare the functional and structural properties of the motor protein, myosin, and isolated myocyte contractility in heart muscle excised from hypertrophic cardiomyopathy patients by surgical myectomy with explanted failing heart and non-failing donor heart muscle. Myosin was isolated and studied using an in vitro motility assay. The distribution of myosin light chain-1 isoforms was measured by two-dimensional electrophoresis. Myosin light chain-2 phosphorylation was measured by sodium dodecyl sulphate-polyacrylamide gel electrophoresis using Pro-Q Diamond phosphoprotein stain. The fraction of actin filaments moving when powered by myectomy myosin was 21% less than with donor myosin (P = 0.006), whereas the sliding speed was not different (0.310 +/- 0.034 for myectomy myosin vs. 0.305 +/- 0.019 microm/s for donor myosin in six paired experiments). Failing heart myosin showed 18% reduced motility. One myectomy myosin sample produced a consistently higher sliding speed than donor heart myosin and was identified with a disease-causing heavy chain mutation (V606M). In myectomy myosin, the level of atrial light chain-1 relative to ventricular light chain-1 was 20 +/- 5% compared with 11 +/- 5% in donor he...Continue Reading

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Citations

Mar 23, 2011·Journal of Cardiovascular Translational Research·Steven B Marston
Jul 17, 2013·Heart, Lung & Circulation·Amy LiCristobal G Dos Remedios
Apr 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alexander R LyonJulia Gorelik
Sep 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael J GreenbergJeffrey R Moore
Mar 27, 2013·The Journal of Biological Chemistry·Christopher ToepferMichael A Ferenczi
Feb 13, 2014·ELife·Michael B RadkeDietmar J Manstein
May 31, 2012·Cellular and Molecular Life Sciences : CMLS·Mirco MüllerHans Georg Mannherz
Jun 25, 2008·Journal of Molecular and Cellular Cardiology·Adam M JacquesSteven B Marston
Jul 15, 2015·Bioarchitecture·Sarah M Heissler, James R Sellers
Jan 16, 2013·Journal of Molecular and Cellular Cardiology·Theresia KraftJolanda van der Velden
Jul 10, 2010·Journal of Molecular and Cellular Cardiology·Anita C HoskinsJonathan C Kentish
Jan 27, 2015·Cardiovascular Research·Thomas EschenhagenBjorn C Knollmann
Feb 17, 2009·Journal of Muscle Research and Cell Motility·Adam JacquesSteven B Marston
Jan 28, 2009·Journal of Muscle Research and Cell Motility·Clare E Gallon
Aug 14, 2010·Journal of Muscle Research and Cell Motility·O'Neal CopelandSteven B Marston
Jun 10, 2009·Journal of Muscle Research and Cell Motility·Bridgette ChristopherOzgur Ogut
Jul 13, 2018·International Journal of Molecular Sciences·Steven Marston
Aug 2, 2018·International Journal of Molecular Sciences·Petr G Vikhorev, Natalia N Vikhoreva
Sep 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Trisha TucholskiYing Ge

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Methods Mentioned

BETA
transgenic
biopsies
motility assay
genotyping
electrophoresis
affinity purification
motility assays

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