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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-7-20
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1464-70
pubmed:meshHeading
pubmed-meshheading:20506278-Antigens, CD4, pubmed-meshheading:20506278-Antineoplastic Agents, Phytogenic, pubmed-meshheading:20506278-Dose-Response Relationship, Drug, pubmed-meshheading:20506278-HIV Long Terminal Repeat, pubmed-meshheading:20506278-HeLa Cells, pubmed-meshheading:20506278-Humans, pubmed-meshheading:20506278-Immunoblotting, pubmed-meshheading:20506278-NAD, pubmed-meshheading:20506278-Nicotinamide Phosphoribosyltransferase, pubmed-meshheading:20506278-RNA Interference, pubmed-meshheading:20506278-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20506278-Signal Transduction, pubmed-meshheading:20506278-Sirtuin 1, pubmed-meshheading:20506278-Stilbenes, pubmed-meshheading:20506278-Transcriptional Activation, pubmed-meshheading:20506278-beta-Galactosidase, pubmed-meshheading:20506278-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2010
pubmed:articleTitle
Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat-mediated long terminal repeat transactivation.
pubmed:affiliation
College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100#, District of Chaoyang, Beijing 100124, China. zhanghs@bjut.edu.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't