VDR hypermethylation and HIV‐induced T cell loss

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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 】

Epigeneticscontributestothedevelopmentofvarietyofdiseasesbymodulationofgeneexpression.WeevaluatedtheeffectofHIV‐inducedVDRmethylationonlossofTCs.HIV/TCdisplayedenhancedVDR‐CpGmethylationandincreasedexpressionofDnmt3bbutattenuatedexpressionofVDR.Ademethylatingagent,AZA,inhibitedthiseffectofHIV.HIV/TCalsodisplayedtheactivationoftheRAS,whichwasreversedbyEB(aVDA).Further,HIV/TCsdisplayedenhancedgenerationofROSandinductionofDSBsbutattenuatedDNArepairresponse.However,inthepresenceofAZA,EB,LOS(aRASblocker),Cat,andtempol(freeradicalscavengers),HIV‐inducedTCROSgenerationandinductionofDSBswereattenuatedbutassociatedwithenhancedDNArepair.Additionally,AZA,EB,andLOSprovidedprotectionagainstHIV‐inducedTCapoptosis.ThesefindingssuggestedthatHIV‐inducedTCapoptosiswasmediatedthroughROSgenerationinresponsetoHIV‐inducedVDRmethylationandassociatedactivationoftheRAS...

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