Phosphorylation of αB-crystallin in the myocardium: Analysis of relations with aging and cardiomyopathy

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Abstract

Phosphorylation is a major post-translational modification of αB-crystallin (CryaB) and determines this protein's chaperone activity, intracellular distribution, translocation, and cytoprotective functions. Phosphorylation of CryaB manifests itself as either beneficial or deleterious consequences depending on the extent of phosphorylation and interaction with the cytoskeleton. Herein, for the first time, we compared the age-related alterations of the expression and phosphorylation (on Ser59: pS59) of CryaB in the myocardium of Wistar and senescence-accelerated OXYS rats. The latters, as we demonstrated here, develop cardiomyopathy by the age of 12 months against the background of hypertension. Rats at the age of 20 days, 3, 12, and 24 months were used. The expression of CryaB mRNA (studied by RT-PCR) and of the CryaB protein (analyzed by western blotting) increased with age in the myocardium of both Wistar and OXYS rats, but only at the age of 24 months did their levels become lower in OXYS rats. Phosphorylation of CryaB increased with age in all rats. There was no association of cardiomyopathy with the pS59-CryaB amount in the detergent-soluble fraction either. Moreover, immunostaining of the myocardium revealed that the amount of pS59-CryaB was greater in OXYS rats than in the control animals. This phenomenon was the result of translocation of pS59-CryaB from the detergent-soluble protein fraction to the detergent-insoluble one. The amount of pS59-CryaB in striated sarcomeres (detergent-insoluble) of the myocardium increased with age in both strains but faster in the myocardium of OXYS rats, and its accumulation preceded the development of cardiomyopathy. Translocation of phosphorylated CryaB to sarcomeres affects functional and structural properties (of cardiomyocytes) that are crucial for contractile function and myofibrillar organization and may be an important component of an endogenous mechanism of aging of the myocardium.

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