期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 110, 期 6, 页码 1464-1470出版社
WILEY-LISS
DOI: 10.1002/jcb.22704
关键词
TAT; SIRT1; NAMPT; LTR TRANSACTIVATION; HIV-1
资金
- National Natural Sciences Foundation of China [30800580]
- Beijing Nova Program [2007B014]
- Beijing Natural Science Foundation [5093025]
- National Basic Research Program of China [2009CB930200]
Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV-1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide(+) (NAD(+))-dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the conversion of nicotinamide into NAD(+), which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat-regulated SIRT activity was studied in Hela-CD4-beta-gal (MAGI) cells. We demonstrated that Tat caused NAD(+) depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat-induced NAD(+) depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat-induced inhibition of SIRT1 activity was potentiated in Nampt-knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat-induced HIV-1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat-induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV-1 infection. J. Cell. Biochem. 110: 1464-1470, 2010. (C) 2010 Wiley-Liss, Inc.
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