Linked Life Data

20623531

Source:http://linkedlifedata.com/resource/pubmed/id/20623531

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-7-13
pubmed:abstractText
Mutations in the superoxide dismutase 1 (SOD1) gene are linked to glutamate excitotoxicity in familial amyotrophic lateral sclerosis (fALS), but the underlying mechanism remains unclear. We investigated whether nuclear factor-kappaB (NF-kappaB) activation is involved in glutamate excitotoxicity by using motor neuron-neuroblastoma hybrid cells that expressed a mutant (G93A) SOD1 (mtSOD1) or wild-type SOD1 (wtSOD1). MtSOD1 cells were more vulnerable to glutamate excitotoxicity than wtSOD1 cells and showed higher NF-kappaB activity, higher nuclear cRel expression, and lower nuclear RelA expression under basal conditions. Glutamate treatment increased NF-kappaB activation along with nuclear expressions of RelA and cRel in wtSOD1 cells but induced only weak nuclear RelA expression in mtSOD1 cells. Suppression of NF-kappaB activation using transfection of the superrepressive mutant form of IkappaBalpha (mIkappaBalpha) inhibited nuclear RelA expression in both types of SOD1 cells, which increased glutamate excitotoxicity in wtSOD1 cells but not in mtSOD1 cells. Furthermore, immunohistochemistry confirmed stronger RelA immunoreactivity in the nuclei of motor neurons of spinal cord in wild-type SOD1 transgenic mice than in those in SOD1 G93A transgenic mice. In addition, we found that glutamate treatment decreased XIAP expression and increased caspase-3 activity in mtSOD1 cells and mIkappaBalpha-overexpressing wtSOD1 cells. Our results suggest that glutamate excitotoxicity in motor neurons of SOD1-linked fALS is attributable, at least in part, to the impairment of IkappaBalpha-dependent RelA activation and subsequent apoptosis mediated by XIAP inhibition and caspase-3 activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1097-4547
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2494-503
pubmed:meshHeading
pubmed-meshheading:20623531-Animals, pubmed-meshheading:20623531-Biotransformation, pubmed-meshheading:20623531-Caspase 3, pubmed-meshheading:20623531-Cell Death, pubmed-meshheading:20623531-Cell Line, pubmed-meshheading:20623531-Cell Nucleus, pubmed-meshheading:20623531-Cell Survival, pubmed-meshheading:20623531-Cytoplasm, pubmed-meshheading:20623531-Fluorescent Dyes, pubmed-meshheading:20623531-Genetic Vectors, pubmed-meshheading:20623531-Glutamic Acid, pubmed-meshheading:20623531-Humans, pubmed-meshheading:20623531-Hybrid Cells, pubmed-meshheading:20623531-Immunohistochemistry, pubmed-meshheading:20623531-Indoles, pubmed-meshheading:20623531-Luciferases, pubmed-meshheading:20623531-Mice, pubmed-meshheading:20623531-Mice, Transgenic, pubmed-meshheading:20623531-Motor Neurons, pubmed-meshheading:20623531-Mutation, pubmed-meshheading:20623531-NF-kappa B, pubmed-meshheading:20623531-Neuroblastoma, pubmed-meshheading:20623531-Receptors, Glutamate, pubmed-meshheading:20623531-Retroviridae, pubmed-meshheading:20623531-Superoxide Dismutase
pubmed:year
2010
pubmed:articleTitle
Impairment of nuclear factor-kappaB activation increased glutamate excitotoxicity in a motoneuron-neuroblastoma hybrid cell line expressing mutant (G93A) Cu/Zn-superoxide dismutase.
pubmed:affiliation
Department of Anatomy and Neurosciences, Eulji University School of Medicine, Daejon, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't