Linked Life Data

16539678

Source:http://linkedlifedata.com/resource/pubmed/id/16539678

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-4-25
pubmed:abstractText
Impaired inflammatory functions may be critical factors in the mechanisms of severe CNS disorders classified as the human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD). Evidence indicates that a viral gene product, the transactivator of transcription protein (Tat), can markedly contribute to these events. We herein report that sulfated polymannuroguluronate (SPMG), a novel anti-acquired immunodeficiency syndrome drug candidate now in a phase II clinical trial, significantly reversed Tat-induced release of pro-inflammatory cytokines [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta) and IL-6] and dose dependently decreased the accumulation of reactive oxygen species and nitric oxide in THP-1 cells. Furthermore, SPMG potently arrested Tat-triggered protein kinase C (PKC)-dependent PKC-mu activation, and blocked the downstream extracellular-signal regulated kinase 1/2- and c-jun amino-terminal kinase-mediated signalling pathways. These molecular mechanisms could be attributed to the fact that SPMG preferentially bound to the basic domain (amino acids 47-57) of the Tat protein with high affinity (K(D) approximately 8.69 x 10(-10) m), leading to abrogation of Tat-mediated neuroinflammation and neurotoxicity. These data demonstrate that SPMG might serve as a valuable therapeutic intervention for Tat-induced profound pro-inflammatory effects in the brain, and subsequent pathologic events of HAD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
334-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16539678-Acquired Immunodeficiency Syndrome, pubmed-meshheading:16539678-Binding Sites, pubmed-meshheading:16539678-Blotting, Western, pubmed-meshheading:16539678-Cell Line, pubmed-meshheading:16539678-Computer Simulation, pubmed-meshheading:16539678-Cytokines, pubmed-meshheading:16539678-Dose-Response Relationship, Drug, pubmed-meshheading:16539678-Drug Interactions, pubmed-meshheading:16539678-Enzyme Activation, pubmed-meshheading:16539678-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16539678-Gene Products, tat, pubmed-meshheading:16539678-Humans, pubmed-meshheading:16539678-Inflammation, pubmed-meshheading:16539678-MAP Kinase Kinase 4, pubmed-meshheading:16539678-Models, Biological, pubmed-meshheading:16539678-Monocytes, pubmed-meshheading:16539678-Nitric Oxide, pubmed-meshheading:16539678-Polysaccharides, pubmed-meshheading:16539678-Reactive Oxygen Species, pubmed-meshheading:16539678-Signal Transduction, pubmed-meshheading:16539678-Time Factors, pubmed-meshheading:16539678-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2006
pubmed:articleTitle
Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome drug candidate, blocks neuroinflammatory signalling by targeting the transactivator of transcription (Tat) protein.
pubmed:affiliation
Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China, Qingdao.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't