Differential Expression of Cardiac Titin Isoforms and Modulation of Cellular Stiffness
| Autor: | Yiming Wu, Karoly Trombitás, Henk Granzier, Michiel Helmes, Olivier Cazorla, Alexandra Freiburg, Siegfried Labeit, Mark McNabb, Thomas Centner |
|---|---|
| Přispěvatelé: | Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Heidelberg] (EMBL), Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology [Pullman, WA, USA], Washington State University (WSU), cazorla, olivier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
MESH: Connectin
Physiology Swine Fluorescent Antibody Technique Muscle Proteins 030204 cardiovascular system & hematology MESH: Protein Isoforms Sarcomere Mice 0302 clinical medicine Diastole Gene expression Myocyte Protein Isoforms Connectin Electrophoresis Gel Two-Dimensional MESH: Animals MESH: Swine MESH: Fluorescent Antibody Technique ComputingMilieux_MISCELLANEOUS 0303 health sciences biology MESH: Diastole Cardiac muscle Heart musculoskeletal system Cell biology [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Actinin alpha 2 medicine.anatomical_structure cardiovascular system [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Titin Cardiology and Cardiovascular Medicine Gene isoform medicine.medical_specialty animal structures MESH: Myocardium MESH: Rats Blotting Western Obscurin 03 medical and health sciences MESH: Muscle Proteins [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Internal medicine [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] medicine Animals MESH: Blotting Western [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph] MESH: Mice MESH: Protein Kinases 030304 developmental biology Myocardium [PHYS.MECA.BIOM] Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph] MESH: Electrophoresis Gel Two-Dimensional Elasticity Rats MESH: Heart Endocrinology biology.protein MESH: Elasticity Protein Kinases |
| Zdroj: | Circulation Research Circulation Research, American Heart Association, 2000, 86 (1), pp.59-67. ⟨10.1161/01.RES.86.1.59⟩ Circulation Research, 2000, 86 (1), pp.59-67. ⟨10.1161/01.RES.86.1.59⟩ |
| ISSN: | 0009-7330 1524-4571 |
| DOI: | 10.1161/01.RES.86.1.59⟩ |
| Popis: | Abstract —Extension of the I-band segment of titin gives rise to part of the diastolic force of cardiac muscle. Previous studies of human cardiac titin transcripts suggested a series of differential splicing events in the I-band segment of titin leading to the so-called N2A and N2B isoform transcripts. Here we investigated titin expression at the protein level in a wide range of mammalian species. Results indicate that the myocardium coexpresses 2 distinct titin isoforms: a smaller isoform containing the N2B element only (N2B titin) and a larger isoform with both the N2B and N2A elements (N2BA titin). The expression ratio of large N2BA to small N2B titin isoforms was found to vary greatly in different species; eg, in the left ventricle the ratio is ≈0.05 in mouse and ≈1.5 in pig. Differences in the expression ratio were also found between atria and ventricles and between different layers of the ventricular wall. Immunofluorescence experiments with isoform-specific antibodies suggest that coexpression of these isoforms takes place at the single-myocyte level. The diastolic properties of single cardiac myocytes isolated from various species expressing high levels of the small (rat and mouse) or large (pig) titin isoform were studied. On average, pig myocytes are significantly less stiff than mouse and rat myocytes. Gel analysis indicates that this result cannot be explained by varying amounts of titin in mouse and pig myocardium. Rather, low stiffness of pig myocytes can be explained by its high expression level of the large isoform: the longer extensible region of this isoform results in a lower fractional extension for a given sarcomere length and hence a lower force. Implications of our findings to cardiac function are discussed. |
| Databáze: | OpenAIRE |
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