| First Author | Cosper PF | Year | 2012 |
| Journal | Am J Pathol | Volume | 181 |
| Issue | 6 | Pages | 2038-46 |
| PubMed ID | 23058369 | Mgi Jnum | J:190726 |
| Mgi Id | MGI:5449510 | Doi | 10.1016/j.ajpath.2012.08.040 |
| Citation | Cosper PF, et al. (2012) Interferon-gamma causes cardiac myocyte atrophy via selective degradation of myosin heavy chain in a model of chronic myocarditis. Am J Pathol 181(6):2038-46 |
| abstractText | Interferon-gamma (IFN-gamma), a proinflammatory cytokine, has been implicated in the pathogenesis of a number of forms of heart disease including myocarditis and congestive heart failure. In fact, overexpression of IFN-gamma in mice causes dilated cardiomyopathy. However, the direct effects of IFN-gamma on cardiac myocytes and the mechanism by which it causes cardiac dysfunction have not been described. Here, we present the molecular pathology of IFN-gamma exposure and its effect on myofibrillar proteins in isolated neonatal rat ventricular myocytes. Treatment with IFN-gamma caused cardiac myocyte atrophy attributable to a specific decrease in myosin heavy chain protein. This selective degradation of myosin heavy chain was not accompanied by a decrease in total protein synthesis or by an increase in total protein degradation. IFN-gamma increased both proteasome and immunoproteasome activity in cardiac myocytes and their inhibition blocked myosin heavy chain loss and myocyte atrophy, whereas inhibition of the lysosome or autophagosome did not. Collectively, these results provide a mechanism by which IFN-gamma causes cardiac pathology in the setting of chronic inflammatory diseases. |
