Linked Life Data

21172429

Source:http://linkedlifedata.com/resource/pubmed/id/21172429

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-2-1
pubmed:abstractText
Up-regulation of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by the HIV-1 transactivator of transcription (Tat) in activated microglia and astrocytes may play a pivotal role during the development of AIDS-related encephalitis and dementia. Previous studies demonstrated that HIV-1 Tat-induced up-regulation of adhesion molecules was mediated by reactive oxygen species (ROS), although the mechanisms underlying HIV-1 Tat-induced ROS generation are unknown. In this study, we examined the possible role of NADPH oxidase in HIV-1 Tat-induced up-regulation of adhesion molecules in astroglioma cell lines. HIV-1 Tat-induced up-regulation of VCAM-1/ICAM-1 and subsequent increased adhesion of monocytes to astrocytes were blocked by a general NADPH oxidase inhibitor, diphenylene iodonium, and a specific inhibitor of NADPH oxidase assembly, 9R3A-gp91ds. Nox2 knockdown using small interfering RNA (siRNA) inhibited HIV-1 Tat-induced up-regulation of adhesion molecules and subsequent increased adhesion of monocytes to astrocytes. Nox2 siRNA blocked HIV-1 Tat-induced ROS production, increase in NADPH oxidase activity, and Rac1 activation. Furthermore, Nox2 siRNA decreased HIV-1 Tat-induced NF-?B activation as well as activation of MAP kinases including ERK, JNK, and p38. These data indicate that Nox2-based NADPH oxidase is responsible for HIV-1 Tat-induced generation of ROS and plays an important role in the up-regulation of adhesion molecules such as VCAM-1/ICAM-1 and subsequent increased adhesion of monocytes to astrocytes and serves as a novel target for HIV-1 Tat-mediated neurological diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-4596
pubmed:author
pubmed:copyrightInfo
2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
576-84
pubmed:meshHeading
pubmed-meshheading:21172429-AIDS Dementia Complex, pubmed-meshheading:21172429-Astrocytes, pubmed-meshheading:21172429-Cell Adhesion, pubmed-meshheading:21172429-Cell Line, Tumor, pubmed-meshheading:21172429-Gene Knockdown Techniques, pubmed-meshheading:21172429-HIV-1, pubmed-meshheading:21172429-Humans, pubmed-meshheading:21172429-Intercellular Adhesion Molecule-1, pubmed-meshheading:21172429-Membrane Glycoproteins, pubmed-meshheading:21172429-Monocytes, pubmed-meshheading:21172429-NADPH Oxidase, pubmed-meshheading:21172429-Onium Compounds, pubmed-meshheading:21172429-RNA, Small Interfering, pubmed-meshheading:21172429-Reactive Oxygen Species, pubmed-meshheading:21172429-Up-Regulation, pubmed-meshheading:21172429-Vascular Cell Adhesion Molecule-1, pubmed-meshheading:21172429-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2011
pubmed:articleTitle
Nox2-based NADPH oxidase mediates HIV-1 Tat-induced up-regulation of VCAM-1/ICAM-1 and subsequent monocyte adhesion in human astrocytes.
pubmed:affiliation
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't