Titin-isoform dependence of titin-actin interaction and its regulation by S100A1/Ca2+ in skinned myocardium.

Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing o...

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Publicado en:Journal of Biomedicine & Biotechnology pp. 727239 - 727240
Autores principales: Fukushima H, Chung CS, Granzier H
Formato: research Journal Article
Publicado: Wiley-Blackwell 2010
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2010
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: Titin-isoform dependence of titin-actin interaction and its regulation by S100A1/Ca2+ in skinned myocardium.
      aug:
        au:
          Fukushima H
          Chung CS
          Granzier H
        affil: Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, PO Box 245217, Tucson, AZ 85724, USA.
      sug:
        subj:
          Calcium Binding Proteins Metabolism
          Calcium Metabolism
          Muscle Proteins Metabolism
          Myocardium Metabolism
          Protein Kinases Metabolism
          Analysis of Variance
          Animal Studies
          Cattle
          Elasticity
          Heart Atrium
          Heart Atrium Metabolism
          Heart Ventricle
          Heart Ventricle Metabolism
          Male
          Mice
          Microfilament Proteins Pharmacodynamics
          Muscle Tonus Drug Effects
          Myocardium
          Proteins
          Male
      ab: Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isoforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a 'viscous break' that is on during diastole and off during systole.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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