title: HDAC1/NFκB pathway is involved in curcumin inhibiting of Tat-mediated long terminal repeat transactivation.
abstract: Chromatin remodeling, especially in relation to the transactivator Tat, is an essential event for human immunodeficiency virus-1 (HIV-1) transcription. Curcumin has been shown to suppress pathways linked to HIV-1 replication. We investigated whether curcumin had the potential to inhibit Tat-induced long terminal repeat region (LTR) transactivation. As we shown, curcumin inhibited Tat-induced LTR transcativation, while knockdown of histone deacetylase 1 (HDAC1) by siRNA potentiated Tat-induced HIV-1 transcativation. Curcumin reversed Tat-induced down-regulation of HDAC1 expression in multinuclear activation of galactosidase indicator (MAGI) cells. Treatment with curcumin reversed Tat-induced dissociation of HDAC1 from LTR; and curcumin caused a decline in the binding of p65/NFκB to LTR promoters stimulated by Tat. Curcumin attenuated Tat-induced p65 phosphorylation and IKK phosphorylation. Curcumin reversed Tat-mediated reduction in AMPK activation and downstream acetyl-CoA carboxylase (ACC) activation. Collectively, our data provide new insights into understanding of the molecular mechanisms of curcumin inhibited Tat-regulated transcription, suggesting that targeting AMPK/HDAC1/NFκB pathway could serve as new anti-HIV-1 agents.
authors.affiliation: College of Life Science & Bioengineering, Beijing University of Technology, Beijing, China. zhanghs@bjut.edu.cn
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ruan
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Sang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000107:Acetylation; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001665:Binding Sites; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D006657:Histones; C498143:RELA protein, human; D051996:Transcription Factor RelA; D054322:tat Gene Products, Human Immunodeficiency Virus; D050880:p300-CBP Transcription Factors; D051550:I-kappa B Kinase; D055372:AMP-Activated Protein Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D000103:Acetyl-CoA Carboxylase; D003474:Curcumin