title: 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.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Dong
authors.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Fenyong
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China. Electronic address: zhoujun@wust.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Biological Medicine, and Medical School, Wuhan University of Science and Technology, Wuhan, Hubei 430065, China; Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: zhangtongcun@wust.edu.cn.
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D017874:Immediate-Early Proteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology / Q000821:virology*; D009687:Nuclear Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin; C069186:IE2 protein, Cytomegalovirus
keywords: Apoptosis; CArG box; Cytomegalovirus immediate early protein; Myocardin; Transactivity