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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Tanshinone II A inhibits tat-induced HIV-1 transactivation through redox-regulated AMPK/Nampt pathway.

Abstract Source:

J Cell Physiol. 2014 Sep ;229(9):1193-201. PMID: 24414799

Abstract Author(s):

Hong-Sheng Zhang, Xin-Yu Chen, Tong-Chao Wu, Feng-Juan Zhang

Article Affiliation:

Hong-Sheng Zhang

Abstract:

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.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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