Linked Life Data

17078933

Source:http://linkedlifedata.com/resource/pubmed/id/17078933

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-11-27
pubmed:abstractText
Human immunodeficiency virus (HIV)-1 infection of the central nervous system occurs in the vast majority of HIV-infected patients. HIV-associated dementia (HAD) represents the most severe form of HIV-related neuropsychiatric impairment and is associated with neuropathology involving HIV proteins and activation of proinflammatory cytokine circuits. Interferon-gamma (IFN-gamma) activates the JAK/STAT1 pathway, a key regulator of inflammatory and apoptotic signaling, and is elevated in HIV-1-infected brains progressing to HAD. Recent reports suggest green tea-derived (-)-epigallocatechin-3-gallate (EGCG) can attenuate neuronal damage mediated by this pathway in conditions such as brain ischemia. In order to investigate the therapeutic potential of EGCG to mitigate the neuronal damage characteristic of HAD, IFN-gamma was evaluated for its ability to enhance well-known neurotoxic properties of HIV-1 proteins gp120 and Tat in primary neurons and mice. Indeed, IFN-gamma enhanced the neurotoxicity of gp120 and Tat via increased JAK/STAT signaling. Additionally, primary neurons pretreated with a JAK1 inhibitor, or those derived from STAT1-deficient mice, were largely resistant to the IFN-gamma-enhanced neurotoxicity of gp120 and Tat. Moreover, EGCG treatment of primary neurons from normal mice reduced IFN-gamma-enhanced neurotoxicity of gp120 and Tat by inhibiting JAK/STAT1 pathway activation. EGCG was also found to mitigate the neurotoxic properties of HIV-1 proteins in the presence of IFN-gamma in vivo. Taken together, these data suggest EGCG attenuates the neurotoxicity of IFN-gamma augmented neuronal damage from HIV-1 proteins gp120 and Tat both in vitro and in vivo. Thus EGCG may represent a novel natural copound for the prevention and treatment of HAD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
1123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
216-25
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17078933-AIDS Dementia Complex, pubmed-meshheading:17078933-Analysis of Variance, pubmed-meshheading:17078933-Animals, pubmed-meshheading:17078933-Apoptosis, pubmed-meshheading:17078933-Catechin, pubmed-meshheading:17078933-Cells, Cultured, pubmed-meshheading:17078933-Female, pubmed-meshheading:17078933-Gene Products, tat, pubmed-meshheading:17078933-HIV Envelope Protein gp120, pubmed-meshheading:17078933-HIV-1, pubmed-meshheading:17078933-Interferon-gamma, pubmed-meshheading:17078933-Janus Kinases, pubmed-meshheading:17078933-Male, pubmed-meshheading:17078933-Mice, pubmed-meshheading:17078933-Mice, Inbred C57BL, pubmed-meshheading:17078933-Mice, Knockout, pubmed-meshheading:17078933-Neurons, pubmed-meshheading:17078933-Neuroprotective Agents, pubmed-meshheading:17078933-Neurotoxins, pubmed-meshheading:17078933-STAT1 Transcription Factor, pubmed-meshheading:17078933-Signal Transduction, pubmed-meshheading:17078933-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2006
pubmed:articleTitle
EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-gamma: role of JAK/STAT1 signaling and implications for HIV-associated dementia.
pubmed:affiliation
Neuroimmunology Laboratory, Silver Child Development Center, Institute for Research in Psychiatry, Department of Psychiatry and Behavioral Medicine, University of South Florida, 3515 East Fletcher Avenue Tampa, FL 33613, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural