Linked Life Data

19720090

Source:http://linkedlifedata.com/resource/pubmed/id/19720090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2009-10-30
pubmed:abstractText
Transcription of human immunodeficiency virus (HIV-1) is activated by viral Tat protein which regulates HIV-long terminal repeat (LTR) transcription and elongation. HIV-1 Tat protein is a substrate for the deacetylase activity of sirtuin 1 (SIRT1). Here we investigate the signaling pathway involved in Tat-induced HIV-1 transactivation through SIRT1. Western blot analysis showed a significant reduction in AMPK activation and downstream acetyl-CoA carboxylase (ACC) activation in response to Tat treatment. NAD(+) levels and SIRT1 activity were also decreased with Tat treatment. SIRT1 activator resveratrol reversed Tat-mediated reduction in AMPK activation and downstream ACC activation; while SIRT1 inhibitor nicotinamide or knockdown of SIRT1 by siRNA potentiated Tat-mediated reduction in AMPK activation and downstream ACC activation. Consistent with this association, AMPK activator AICAR as well as resveratrol inhibited Tat-induced HIV-1 transactivation. On the contrary, AMPK inhibitor compound C, knockdown of AMPK by siRNA as well as nicotinamide or knockdown of SIRT1 by siRNA potentiated Tat-induced HIV-1 transactivation. Collectively, our data provide new insights into understanding of the molecular mechanisms of Tat-regulated transcription, suggesting that targeting SIRT1-AMPK pathway could serve as a new target for the development of new anti HIV-1 agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Acetyl-CoA Carboxylase, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/NAD, http://linkedlifedata.com/resource/pubmed/chemical/Niacinamide, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/SIRT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Sirtuin 1, http://linkedlifedata.com/resource/pubmed/chemical/Stilbenes, http://linkedlifedata.com/resource/pubmed/chemical/resveratrol, http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1872-7492
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
146
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
SIRT1 regulates Tat-induced HIV-1 transactivation through activating AMP-activated protein kinase.
pubmed:affiliation
Department of Virology & Pharmacology, 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