The ubiquitin-proteasome system is enhanced in degenerating cardiomyocytes of dilated cardiomyopathy

Abstract

To maintain intracellular homeostasis against cellular stresses, proteins are not only synthesized but also degraded by proteolytic mechanisms. The ubiquitin (Ub)-proteasome system is the most important mechanism to select and digest damaged intracellular proteins. However, it is still unclear how the Ub-proteasome system plays a role in the failing heart. To elucidate the expressions of Ub and proteasomes in the myocardium of dilated cardiomyopathy (DCM), myocardial tissue obtained from nineteen DCM patients at the left ventriculoplasty was studied. Four normal autopsied hearts served as control. Immunohistochemistry revealed that both Ub and proteasomes were very weak in controls and in less degenerated cardiomyocytes of DCM hearts. On the other hand, their expressions were markedly enhanced in vesicles accumulated adjacent to nuclei, periphery of large vacuoles, hyaline materials and disorganized cytoplasm of degenerated cardiomyocytes. The quantitative analysis of percent area showed that expression of Ub and proteasome were statistically higher in DCM hearts than in normal controls. We propose that the Ub-proteasome system may be protectively enhanced to disorganize damaged proteins and reduce their toxicity. However, it is also possible that the Ub-proteasome system, when its expression is massive, may associate with cytoplasmic degeneration preceding cell death. In conclusion, proteolysis by the Ub-proteasome system is enhanced under the condition where cardiomyocyte degeneration is processing in DCM hearts.