Remodeling of dystrophin-glycoprotein complex, intercalated disk proteins, and contractile proteins in the hearts of mice subjected to sepsis induced by cecal ligation and puncture. / Remodelamento do complexo de glicoproteínas associadas à distrofina, do disco intercalar e das proteínas contráteis no coração de camundongos submetidos à sépsis induzida por ligação e perfuração do ceco

AUTOR(ES)

Mara Rubia Nunes Celes

DATA DE PUBLICAÇÃO

2008

RESUMO

Sepsis and septic shock represent a complex syndrome of systemic inflammatory response, with multiple physiological and immunological abnormalities, commonly caused by bacterial infection. The most important consequence of the response is the involvement of many organs and tissues. Cardiac dysfunction, caused by impairment in myocardial contractility, has been recognized as an important factor that contributes to the high mortality observed in sepsis. Evidence from our laboratory indicates that myocardial structural changes could be responsible for sepsis-induced myocardial dysfunction. Taking into account that the contractile machinery inside the myofibers must remain intimately connected with the membrane and extracellular matrix, the present investigation sought to evaluate changes in intercellular communications and mechanical coupling between the neighbor cardiomyocytes and the expression of the cell scaffold protein and extracellular matrix (specifically merosin laminin-2 chain) during the severe sepsis. Our results showed a decrease in the expression of proteins involved in formation of gap junctions (connexin-43) and adherens junctions (N-cadherin). These alterations may result in the loss of intercalated disc structural integrity, changing the mechanical and electrical-chemical coupling between neighboring cardiomyocytes. Additionally, we demonstrated the decrease of dystrophin and dystrophin-glycoprotein complex (DGC) components resulting from severe septic injury. The reduction or loss of dystrophin is the primary event that occurs followed by miofilamentar degeneration characterized by actin and myosin lysis. The decrease of glycoproteins associated with dystrophin: -dystroglican and laminin were considered secondary events. The results suggest that during experimental severe sepsis induced by cecal ligation and puncture (CLP), there is loss of important proteins involved in both the remodeling of the intercalated disc and the glycoproteins expression implicated in the mechanical link between the intracellular cytoskeleton and extracellular matrix. Although the functional studies are needed to determine the direct effect of these alterations on myocardium, we can suggest that myocardial structural changes may be partly responsible for sepsis-induced cardiac depression.

ASSUNTO(S)

sepsis/choque séptico complexo de glicoproteínas associadas à distrofina proteínas contráteis dystrophin-glycoprotein complex adherens junctions disco intercalar dystrophin myosin. miocárdio gap junctions intercalated disc severe sepsis actin septic shock clp myocardial dysfunction

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