scholarly journals Desensitization of Myofilaments to Ca 2+ as a Therapeutic Target for Hypertrophic Cardiomyopathy With Mutations in Thin Filament Proteins

2014 ◽  
Vol 7 (2) ◽  
pp. 132-143 ◽  
Author(s):  
Marco L. Alves ◽  
Fernando A.L. Dias ◽  
Robert D. Gaffin ◽  
Jillian N. Simon ◽  
Eric M. Montminy ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Therapeutic Target ◽  
Thin Filament ◽  
Thin Filament Proteins

scholarly journals Spaceflight results in increase of thick filament but not thin filament proteins in the paramyosin mutant of Caenorhabditis elegans

2008 ◽  
Vol 41 (5) ◽  
pp. 816-823 ◽  
Author(s):  
R. Adachi ◽  
T. Takaya ◽  
K. Kuriyama ◽  
A. Higashibata ◽  
N. Ishioka ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Thin Filament ◽  
Thick Filament ◽  
Thin Filament Proteins

scholarly journals Cardiomyopathy: Getting Bigger All the Time - Lessons Learned about Heart Disease from Tropomyosin

2021 ◽  
Author(s):  
David F. Wieczorek
Keyword(s):  
Heart Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Genetic Association ◽  
Basic Science ◽  
Thin Filament ◽  
Contractile Proteins ◽  
Lessons Learned ◽  
Genetic Mutations ◽  
Filament Protein ◽  
Science Investigations

In 1990, John and Christine Seidman uncovered the genetic association between mutations in sarcomeric contractile proteins and hypertrophic cardiomyopathy. Since then, the increase in knowledge and understanding of this disease has increased exponentially. Although pathologies associated with the various cardiomyopathies are vastly different, in some cases, the same proteins are causative, but with different genetic mutations. The focus of this article will be on hypertrophic and dilated cardiomyopathies, which are often caused by mutations in sarcomeric contractile proteins. Tropomyosin, a thin filament protein, serves as a paradigm to illustrate how different mutations within the same protein can generate the hypertrophic or dilated cardiomyopathic condition. As such, the significant advances in information derived from basic science investigations has led to the development of novel therapeutics in the treatment of these pathological diseases. This article will illustrate linkages which occur to bridge scientific advances to clinical treatments in cardiomyopathic patients.

scholarly journals KLHL40 deficiency destabilizes thin filament proteins and promotes nemaline myopathy

2014 ◽  
Vol 124 (8) ◽  
pp. 3529-3539 ◽  
Author(s):  
Ankit Garg ◽  
Jason O’Rourke ◽  
Chengzu Long ◽  
Jonathan Doering ◽  
Gianina Ravenscroft ◽  
...  
Keyword(s):  
Thin Filament ◽  
Nemaline Myopathy ◽  
Thin Filament Proteins

Expression of Fast Thin Filament Proteins. Defining Fiber Archetypes in a Molecular Continuum

1990 ◽  
pp. 279-292 ◽  
Author(s):  
Fred Schachat ◽  
Margaret M. Briggs ◽  
Edward K. Williamson ◽  
Hirschel McGinnis ◽  
Michael S. Diamond ◽  
...  
Keyword(s):  
Thin Filament ◽  
Thin Filament Proteins

Pig platelet tropomyosin: Interactions with the other thin-filament proteins

1986 ◽  
Vol 192 (4) ◽  
pp. 815-830 ◽  
Author(s):  
G. Pruliere ◽  
S.D. Fuller ◽  
A.G. Weeds ◽  
A. d'Albis ◽  
E. der Terrossian
Keyword(s):  
Thin Filament ◽  
The Other ◽  
Thin Filament Proteins

Doxorubicin and covalently crosslinked doxorubicin derivatives binding to purified cardiac thin-filament proteins in vitro

1985 ◽  
Vol 43 (1) ◽  
pp. 64-73 ◽  
Author(s):  
William Lewis ◽  
Kevin Beckenstein ◽  
Lawrence Shapiro ◽  
Saul Puszkin
Keyword(s):  
Thin Filament ◽  
Thin Filament Proteins

scholarly journals The Actc A295S Hypertrophic Cardiomyopathy Mutation Promotes Thin Filament Disinhibition and Enhances Contractile Activity

2017 ◽  
Vol 112 (3) ◽  
pp. 559a
Author(s):  
Meera C. Viswanathan ◽  
William Schmidt ◽  
Marek Orzechowski ◽  
William Lehman ◽  
Anthony Cammarato
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Thin Filament ◽  
Contractile Activity

Thin Filament Proteins and Thin Filament-Linked Regulation of Vertebrate Muscle Contractio

1984 ◽  
Vol 16 (3) ◽  
pp. 235-305 ◽  
Author(s):  
Paul C. Leavis ◽  
John Gergely ◽  
Andrew G. Szent-Gyorgyi
Keyword(s):  
Thin Filament ◽  
Vertebrate Muscle ◽  
Thin Filament Proteins

Myosin MgADP release rate decreases at longer sarcomere length to prolong myosin attachment time in skinned rat myocardium

2015 ◽  
Vol 309 (12) ◽  
pp. H2087-H2097 ◽  
Author(s):  
Bertrand C. W. Tanner ◽  
Jason J. Breithaupt ◽  
Peter O. Awinda
Keyword(s):  
Release Rate ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Sarcomere Length ◽  
Cardiac Contractility ◽  
Force Production ◽  
Cross Bridge ◽  
Thin Filament Proteins ◽  
Filament Activation ◽  
Ventricular Filling

Cardiac contractility increases as sarcomere length increases, suggesting that intrinsic molecular mechanisms underlie the Frank-Starling relationship to confer increased cardiac output with greater ventricular filling. The capacity of myosin to bind with actin and generate force in a muscle cell is Ca2+ regulated by thin-filament proteins and spatially regulated by sarcomere length as thick-to-thin filament overlap varies. One mechanism underlying greater cardiac contractility as sarcomere length increases could involve longer myosin attachment time ( t on) due to slowed myosin kinetics at longer sarcomere length. To test this idea, we used stochastic length-perturbation analysis in skinned rat papillary muscle strips to measure t on as [MgATP] varied (0.05–5 mM) at 1.9 and 2.2 μm sarcomere lengths. From this t on-MgATP relationship, we calculated cross-bridge MgADP release rate and MgATP binding rates. As MgATP increased, t on decreased for both sarcomere lengths, but t on was roughly 70% longer for 2.2 vs. 1.9 μm sarcomere length at maximally activated conditions. These t on differences were driven by a slower MgADP release rate at 2.2 μm sarcomere length (41 ± 3 vs. 74 ± 7 s−1), since MgATP binding rate was not different between the two sarcomere lengths. At submaximal activation levels near the pCa50 value of the tension-pCa relationship for each sarcomere length, length-dependent increases in t on were roughly 15% longer for 2.2 vs. 1.9 μm sarcomere length. These changes in cross-bridge kinetics could amplify cooperative cross-bridge contributions to force production and thin-filament activation at longer sarcomere length and suggest that length-dependent changes in myosin MgADP release rate may contribute to the Frank-Starling relationship in the heart.

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