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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-7-20
pubmed:abstractText
The relative roles of the high-affinity nerve growth factor (NGF) receptor, TrkA, and low-affinity p75 neurotrophin receptor (p75NTR) in neuronal survival are an active research area. We reported previously that UV treatment induces a calpain-dependent, delayed neuronal death. We show here that NGF inhibits this UV-induced cortical neuron death. Interestingly, NGF neuroprotection requires p75NTR. Because it has been reported that NGF binding to p75NTR leads to ceramide generation, we evaluated whether ceramide was also neuroprotective. We found that ceramide also inhibits UV toxicity, and that the actions of ceramide and NGF were not additive. Moreover, cycloheximide inhibited ceramide and NGF neuroprotection, suggesting that their actions require new protein synthesis. Consistent with this possibility, we found that NGF activates the expression of genes such as calbindin. Lastly, we explored the role of calpain in NGF actions. NGF and ceramide both reduced the level of calpain activation after UV treatment. This NGF effect was p75NTR dependent. Overall, we interpret these results as consistent with an NGF neuroprotective pathway wherein p75NTR activation leads sequentially to ceramide generation, new protein synthesis, and inhibition of calpain activation. Overall, these results provide insight into a p75NTR dependent pathway of NGF neuroprotection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
552-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15264225-Animals, pubmed-meshheading:15264225-Calcium-Binding Protein, Vitamin D-Dependent, pubmed-meshheading:15264225-Calpain, pubmed-meshheading:15264225-Cell Death, pubmed-meshheading:15264225-Cell Survival, pubmed-meshheading:15264225-Cells, Cultured, pubmed-meshheading:15264225-Ceramides, pubmed-meshheading:15264225-Drug Interactions, pubmed-meshheading:15264225-Fetus, pubmed-meshheading:15264225-Gene Expression Regulation, pubmed-meshheading:15264225-Nerve Degeneration, pubmed-meshheading:15264225-Nerve Growth Factor, pubmed-meshheading:15264225-Neuroprotective Agents, pubmed-meshheading:15264225-Protein Synthesis Inhibitors, pubmed-meshheading:15264225-Rats, pubmed-meshheading:15264225-Rats, Sprague-Dawley, pubmed-meshheading:15264225-Receptor, Nerve Growth Factor, pubmed-meshheading:15264225-Receptors, Nerve Growth Factor, pubmed-meshheading:15264225-Ultraviolet Rays
pubmed:year
2004
pubmed:articleTitle
NGF acts via p75 low-affinity neurotrophin receptor and calpain inhibition to reduce UV neurotoxicity.
pubmed:affiliation
Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't