Cytokine G-protein signaling crosstalk in cardiomyocytes: Attentuation of Jak-STAT activation by endothelin-1 |
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Authors: | Booz George W Day Jonathan NE Speth Robert Baker Kenneth M |
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Institution: | (1) Laboratoire de Cardiologie Cellulaire et Moléculaire, INSERM U-446, IFR-75 Institut de Signalisation et Innovation Thérapeutique, Université Paris-Sud, Faculté de Pharmacie, F-92296 Châtenay-Malabry, Cedex, France;(2) Laboratoire de Biochimie et de Biologie Cellulaire, EA 1595, IFR-75 Institut de Signalisation et Innovation Thérapeutique, Université Paris-Sud, Faculté de Pharmacie, F-92296 Châtenay-Malabry, Cedex, France |
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Abstract: | Cytoskeletal reorganization has been shown to participate in cellular remodeling and in the alterations of mechanical function of isolated cardiomyocytes during pressure overload hypertrophy. Post-translational modifications of tubulin towards stabilization of microtubules have also been described in animal models of compensatory hypertrophy, but the status of the microtubules network in end stage heart failure is not clearly established. Using a rat model of congestive heart failure (CHF) induced by aortic banding, we studied the expression of - and -tubulin, as well as their post-translational modification and distribution in the soluble and polymerized fraction by immunoblotting. We found an accumulation of - and -tubulin protein content specifically in the soluble fraction with no change in the polymerized fraction. Amongst the several variants of -tubulin examined, only detyrosinated Glu-tubulin and deglutamylated 2-tubulin levels were selectively increased during heart failure. Glu-tubulin accumulated in the polymerized fraction while 2-tubulin levels were increased in the soluble fraction in CHF hearts. These results show that a profound remodeling of the microtubule network occurs in heart failure. This remodeling suggests an increase in the stability of the microtubule network which is discussed in terms of possible functional consequences. |
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Keywords: | heart failure microtubules post-translational modifications - and gif" alt="agr" align="BASELINE" BORDER="0">- and -tubulin" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0">-tubulin |
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