title: VDR hypermethylation and HIV-induced T cell loss.
abstract: 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.
authors: Immunology Center, Feinstein Institute for Medical Research, Hofstra North Shore-Long Island Jewish Health System School ofMedicine at Hofstra University, Hempstead, New York, USA.
authors: Nirupama
authors: N
authors: Chandel
authors: Mohammad
authors: M
authors: Husain
authors: Hersh
authors: H
authors: Goel
authors: Divya
authors: D
authors: Salhan
authors: Xiqian
authors: X
authors: Lan
authors: Ashwani
authors: A
authors: Malhotra
authors: Joseph
authors: J
authors: McGowan
authors: Pravin C
authors: PC
authors: Singhal
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001374:Azacitidine / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D018655:Lymphocyte Count; D017382:Reactive Oxygen Species / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine; D002117:Calcitriol; D002374:Catalase; D004248:DNA (Cytosine-5-)-Methyltransferases; D004791:Enzyme Inhibitors; D019808:Losartan; D017382:Reactive Oxygen Species; D018167:Receptors, Calcitriol; D018631:ras Proteins; D000097584:DNA Methyltransferase 3B; C078903:seocalcitol
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