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Tanshinone II A Inhibits Tat‐Induced HIV‐1 Transactivation Through Redox‐Regulated AMPK/Nampt Pathway
Author(s) -
Zhang HongSheng,
Chen XinYu,
Wu TongChao,
Zhang FengJuan
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24552
Subject(s) - transactivation , nicotinamide phosphoribosyltransferase , ampk , chemistry , nad+ kinase , microbiology and biotechnology , transcription factor , signal transduction , biochemistry , protein kinase a , phosphorylation , enzyme , biology , gene
Tat transactivating activity regulated by NAD + ‐dependent histone deacetylase sirtuin1 (SIRT1) connects HIV transcription with the metabolic state of the cell. Nicotinamide phosphoribosyltransferase (Nampt) is a rate‐limiting enzyme in the mammalian NAD + biosynthesis. Nampt, SIRT1, and AMPK were involved in inhibiting HIV‐1 transactivation through redox‐regulated pathway. Tanshinone II A is a main lipid‐soluble monomer derivative from the root of Salvia miltiorrhiza (Danshen) and tanshinone II A possess a variety of biological activities through redox signaling pathway. Here we investigated the effect of tanshinone II A on Tat‐induced HIV‐1 transactivation and the redox signaling pathway involved in it. As the results were shown, tanshinone II A reversed Tat‐induced reactive oxygen species (ROS) production and down‐regulation of glutathione (GSH) levels in TZM‐bl cells through up‐regulation of Nrf2 expression. Tanshinone II A reversed Tat‐induced inhibition of SIRT1 activity but not SIRT1 protein expression. Tanshinone II A reversed Tat‐induced inhibition of Nampt protein expression and depletion of NAD + levels in TZM‐bl cells in a dose‐dependent manner. Tanshinone II A‐evoked Nampt expression was mediated by AMPK signaling pathway. Tanshinone II A inhibited Tat‐induced HIV‐1 LTR transactivation dependent on AMPK‐Nampt pathway. Collectively, our data provide new insights into understanding of the molecular mechanisms of tanshinone II A inhibited Tat‐regulated transcription, suggesting that targeting AMPK/Nampt/SIRT1 pathway could serve as new anti‐HIV‐1 agents. J. Cell. Physiol. 229: 1193–1201, 2014. © 2014 Wiley Periodicals, Inc.