VDR hypermethylation and HIV-induced T cell loss

Journal of Leukocyte Biology

Joseph McGowan¹  Hersh Goel¹  Ashwani Malhotra¹  Mohammad Husain¹  Xiqian Lan¹  Divya Salhan¹  Nirupama Chandel¹  Pravin C. Singhal¹ 

[1] Immunology Center, Feinstein Institute for Medical Research, Hofstra North Shore-Long Island Jewish Health System School of Medicine at Hofstra University, Hempstead, New York, USA Immunology Center, Feinstein Institute for Medical Research, Hofstra North Shore-Long Island Jewish Health System School of Medicine at Hofstra University, Hempstead, New York, USA Immunology Center, Feinstein Institute for Medical Research, Hofstra North Shore-Long Island Jewish Health System School of Medicine at Hofstra University, Hempstead, New York, USA

关键词: DNA methyltransferase;    renin angiotensin system;    double-strand break;    reactive oxygen species;   

DOI  :  10.1189/jlb.0812383

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Epigenetics contributes to the development of variety of diseases by modulation of gene expression. We evaluated the effect of HIV-induced VDR methylation on loss of TCs. HIV/TC displayed enhanced VDR-CpG methylation and increased expression of Dnmt3b but attenuated expression of VDR. A demethylating agent, AZA, inhibited this effect of HIV. HIV/TC also displayed the activation of the RAS, which was reversed by EB (a VDA). Further, HIV/TCs displayed enhanced generation of ROS and induction of DSBs but attenuated DNA repair response. However, in the presence of AZA, EB, LOS (a RAS blocker), Cat, and tempol (free radical scavengers), HIV-induced TC ROS generation and induction of DSBs were attenuated but associated with enhanced DNA repair. Additionally, AZA, EB, and LOS provided protection against HIV-induced TC apoptosis. These findings suggested that HIV-induced TC apoptosis was mediated through ROS generation in response to HIV-induced VDR methylation and associated activation of the RAS.

【 授权许可】

Unknown