Isoproterenol Induces Primary Loss of Dystrophin in Rat Hearts: Correlation with Myocardial Injury

Author(s)

Campos, E. C. ; Romano, M. M. D. ; Celes, M. R. N. ; Prado, C. M. ; Rossi, M. A. ; Kimchi, A

• Document type: Journal article
• Source: CURRENT ADVANCES IN HEART DISEASE; v. N/A, p. 2-pg., 2008-01-01.

Abstract

Alterations in the structural integrity of the sarcolemma of cardiomyocytes have been demonstrated to be caused by isoproterenol. Since sarcolemmal integrity is stabilized by the dystrophin-glycoprotein complex (DGC) that connects actin and laminin in contractile machinery and extracellular matrix and by integrins that also are essential to define cellular-extracellular interaction, this study tests the hypothesis that isoproterenol affects sarcolemmal stability through changes in the DGC and integrins. Immunofluorescent staining revealed that dystrophin is the most sensitive among the structures connecting the actin in the cardiomyocyte cytoskeleton and the extracellular matrix represented by laminin in the present study. The sarcomeric actin dissolution, as part of the process of myocytolysis, occurred after dystrophin reduction or loss. Subsequently, after lysis of myofilaments, the expressions of gamma-sarcoglycan, beta-dystroglycan, beta 1-integrin and laminin alpha-2 were reduced followed by their breakdown, as epiphenomena of the myocytolytic process In conclusion, administration of isoproterenol to rats results in primary loss of dystrophin, the most sensitive among the structural proteins of the DGC. These changes, related to ischemic injury, can explain the severe alterations in the structural integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible injury induced by isoproterenol. (AU)