J Bacteriol Virol.  2014 Sep;44(3):261-268. 10.4167/jbv.2014.44.3.261.

Uncleaved Dystrophin Induce Cardiac Myocyte Apoptosis in Coxsackievirus Infected Balb/C Background Mice Heart

Affiliations
  • 1Department of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk, Korea. bklim@jwu.ac.kr

Abstract

It has been previously demonstrated that dystrophin is cleaved in the cardiac myocyte by the viral protease 2A following infection with Coxsackievirus B3 (CVB3). The viral protease 2A mediated cardiomyopathy can be prevented by inhibiting cleavage of dystrophin. However, it is less clear whether uncleaved dysdrophin have other heart protective effect in coxsackievirus infection. To address this, we generated a Balb/C background mouse that had a point mutation in dystrophin that prevents cleavage by protease 2A (KI). We show here that when mice expressing cleavage-resistant dystrophin were infected with CVB3, there was increased cardiac myocyte apoptosis. Bax and Bcl-X(L) mRNA ratio was significantly increased in KI mice heart compare to wild type mice heart. We found cleavage-resistant dystrophin induced the apoptosis related enzyme capspase-3 and caspase-8 activity. In addition, TUNEL stain was observed many TUNEL positive cardiac myocyte in KI mice heart compare to wild type mice heart (3.7% vs 0.3%). However, zVAD treatment for apoptosis blocking was significantly decreased myocardium damage and fibrosis in KI mice heart. These findings indicated that uncleaved dystrophin may have a critical role in cardiac myocyte viral propagation. Uncleaved dystrophin mutant induced cardiac myocyte apoptosis. It delayed coxsackievirus propagation in cardiac myocyte and could prevent cardiac myocyte death.

Keyword

Dystrophin; Cardiac myocyte; Coxsackievirus; Apoptosis; Protease 2A

MeSH Terms

Animals
Apoptosis*
Cardiomyopathies
Caspase 8
Coxsackievirus Infections
Dystrophin*
Fibrosis
Heart*
In Situ Nick-End Labeling
Mice*
Myocardium
Myocytes, Cardiac*
Point Mutation
RNA, Messenger
Caspase 8
Dystrophin
RNA, Messenger
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