Injury-induced NF-kappaB activation in the hippocampus: implications for neuronal survival.
Nuclear factor (NF)-kappaB p50 protein is involved in promoting survival in hippocampal neurons after trimethyltin (TMT)-injury. In the current study, hippocampal NF-kappaB activity was examined and quantitated from transgenic kappaB-lacZ reporter mice after chemical-induced injury. NF-kappaB activity was localized primarily to hippocampal neurons and significantly elevated over that in saline-treated mice between 4 and 21 days after TMT injection. Seven days after TMT injection, a timepoint of elevated NF-kappaB activity, gene expression in the hippocampus was studied by microarray analysis through comparison of expression profiles between treated nontransgenic and p50-null mice with their saline-injected controls. Seventeen genes increased in nontransgenic TMT-treated mice relative to saline-treated as well as showing no increase in p50-null mice, indicating a role for p50 in their regulation. One of these genes, the Na+, K+-ATPase-gamma subunit, was detected in brain for the first time. Several of the genes modulated by NF-kappaB are potentially related to neuroplasticity, providing additional evidence that this transcription factor is a neuroprotective signal in the hippocampus.
Kassed
C A
CA
Department of Pharmacology and Therapeutics, University of South Florida, Tampa, Florida 33612, USA.
Butler
T L
TL
Patton
G W
GW
Demesquita
D D
DD
Navidomskis
M T
MT
Mémet
S
S
Israël
A
A
Pennypacker
K R
KR
D000818:Animals; D002470:Cell Survival; D020862:GC Rich Sequence; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C498816:Fxyd2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase