Human cytomegalovirus immediate early protein 2 enhances myocardin-mediated survival of rat aortic smooth muscle cells.

Abstract

Human cytomegalovirus (HCMV) may increase the incidence of restenosis and predispose to atherosclerosis. The lesions of restenosis and atherosclerosis often contain smooth muscle cells (SMCs) with high rates of proliferation and apoptosis. One of the immediate early (IE) gene products of HCMV-IE2 affects transcriptional activities of some cellular factors in SMCs, including myocardin. In this study, we studied the effects of IE2 and myocardin on PI3K pathway inducer wortmannin induced apoptosis in rat aortic SMCs. We show that the transcriptional activity of myocardin on Mcl-1 promoter is enhanced by co-expression of HCMV IE2 in rat aortic SMCs; and the expressions of mRNA and protein of antiapoptotic genes-Mcl-1 and Bcl-2 are upregulated by IE2 alone and co-transfection of myocardin and IE2, but decreased by myocardin-specific shRNA in rat aortic SMCs. We further demonstrate that co-expression of myocardin and HCMV IE2 declines apoptotic cell numbers and caspase-3 activities induced by serum starvation plus wortmannin in rat aortic SMCs. The results suggest that HCMV IE2 enhances myocardin-mediated survival of rat aortic SMCs under serum deprivation and PI3-kinase inhibition, partly via activation of Mcl-1's antiapoptosis effect. Our study connects HCMV IE2 to myocardin-induced transcriptional program for rat aortic SMCs survival and proliferation, involving in HCMV related restenosis and atherosclerosis.

• Authors: Xing-Hua Liao, Xiumei Dong, Chenyu Wu, Tao Wang, Fenyong Liu, Jun Zhou, Tong-Cun Zhang
• Journal: Virus research (Virus Res) Vol. 192 Pg. 85-91 (Nov 04 2014) ISSN: 1872-7492 [Electronic] Netherlands
• PMID: 25157858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• IE2 protein, Cytomegalovirus
• Immediate-Early Proteins
• Nuclear Proteins
• Trans-Activators
• myocardin

Topics

• Animals
• Cell Proliferation
• Cell Survival
• Cells, Cultured
• Cytomegalovirus (physiology)
• Host-Pathogen Interactions
• Immediate-Early Proteins (metabolism)
• Myocytes, Smooth Muscle (cytology, physiology, virology)
• Nuclear Proteins (metabolism)
• Rats, Sprague-Dawley
• Trans-Activators (metabolism)