Linked Life Data

11943805

Source:http://linkedlifedata.com/resource/pubmed/id/11943805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-10
pubmed:abstractText
Tumor necrosis factor receptor-I (TNFRI) and TNFRII are two TNFR subtypes in the immune system, but their roles in the brain remain unclear. Here we present a novel interaction between TNFR subtypes and TNF-alpha in the brain. Our studies on target-depleted TNFR in mice show that TNF-alpha has little effect on hippocampal neurons in which TNFRI, containing an "intracellular death domain," is absent (TNFRI -/-), whereas neurons from TNFRII knock-out mice are vulnerable to TNF-alpha even at low doses. Moreover, little nuclear factor-kappaB (NF-kappaB) translocation is induced by TNF-alpha in neurons of TNFRI -/-, whereas NF-kappaB subunit p65 is still translocated from the cytoplasm into the nucleus in neurons from wild-type and TNFRII -/- mice. Furthermore, p38 mitogen-activated protein (MAP) kinase activity is upregulated in neurons from both wild-type and TNFRI -/-, but no alteration of p38 MAP kinase was found in neurons from TNFRII. Results from overexpression of TNF receptors further support the above findings. NT2 neuronal-like cells transiently transfected with TNFRI are very sensitive to TNF-alpha, whereas TNF-alpha is not toxic and even seems to be trophic to the cells with TNFRII overexpression. Last, our radioligand-binding experiments demonstrate that TNF-alpha binds TNFRI with high affinity (K(d) of 0.6 nm), whereas TNFRII shows lower binding affinity (K(d) of 1.14 nm) to TNF-alpha in NT2 transfected cells. Together, these studies reveal novel neuronal responses of TNF-alpha in mediating consequences of TNF receptor activation differently. Subsequent neuronal death or survival may ultimately depend on a particular subtype of TNF receptor that is predominately expressed in neurons of the brain during neural development or with neurological diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3025-32
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11943805-Active Transport, Cell Nucleus, pubmed-meshheading:11943805-Animals, pubmed-meshheading:11943805-Antigens, CD, pubmed-meshheading:11943805-Binding, Competitive, pubmed-meshheading:11943805-Cell Death, pubmed-meshheading:11943805-Cell Survival, pubmed-meshheading:11943805-Cells, Cultured, pubmed-meshheading:11943805-Dose-Response Relationship, Drug, pubmed-meshheading:11943805-Gene Expression, pubmed-meshheading:11943805-Gene Targeting, pubmed-meshheading:11943805-Hippocampus, pubmed-meshheading:11943805-In Situ Nick-End Labeling, pubmed-meshheading:11943805-Mice, pubmed-meshheading:11943805-Mice, Inbred C57BL, pubmed-meshheading:11943805-Mice, Knockout, pubmed-meshheading:11943805-Mitogen-Activated Protein Kinases, pubmed-meshheading:11943805-NF-kappa B, pubmed-meshheading:11943805-Neurons, pubmed-meshheading:11943805-Receptors, Tumor Necrosis Factor, pubmed-meshheading:11943805-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:11943805-Receptors, Tumor Necrosis Factor, Type II, pubmed-meshheading:11943805-Signal Transduction, pubmed-meshheading:11943805-Transfection, pubmed-meshheading:11943805-Tumor Necrosis Factor-alpha, pubmed-meshheading:11943805-p38 Mitogen-Activated Protein Kinases
pubmed:year
2002
pubmed:articleTitle
Target depletion of distinct tumor necrosis factor receptor subtypes reveals hippocampal neuron death and survival through different signal transduction pathways.
pubmed:affiliation
Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, Arizona 85351, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't