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.
Copyright © 2011 Wiley-Liss, Inc.