Post-translational modifications of cardiac tubulin during chronic heart failure in the rat.

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 alpha- and beta-tubulin, as well as their post-translational modification and distribution in the soluble and polymerized fraction by immunoblotting. We found an accumulation of alpha- and beta-tubulin protein content specifically in the soluble fraction with no change in the polymerized fraction. Amongst the several variants of alpha-tubulin examined, only detyrosinated Glu-tubulin and deglutamylated delta2-tubulin levels were selectively increased during heart failure. Glu-tubulin accumulated in the polymerized fraction while delta2-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.