NF-kappaB p50 is increased in neurons surviving hippocampal injury.
Signal transduction pathways that lead to the modulation of genes related to survival and repair mechanisms are activated in neurons that survive injury. These protein kinase/phosphatase cascades converge on transcription factors, the DNA binding proteins that directly regulate gene expression. In this study we examined expression of the NF-kappaB p50 subunit in the rat hippocampus 7 days after injury caused by middle cerebral artery occlusion or trimethyltin treatment. We found increased levels of p50 in neurons throughout the hippocampus after both treatments, localized not only in cell bodies but also in processes. At the 7-day time point, Fluoro-Jade histochemistry revealed hippocampal neurodegeneration in trimethyltin-treated rats but not in those lesioned by middle cerebral artery occlusion. p50 was not expressed in Fluoro-Jade-positive degenerating cells, supporting the role of this transcriptional subunit in neurosurvival. Because phosphorylation of the inhibitor IkappaB protein by IkappaB kinase is the classic step in NF-kappaB activation, phospho-IkappaBalpha immunoreactivity was examined as an indication of IkappaB kinase activity. Levels of phospho-IkappaBalpha were increased in neurons throughout the hippocampus 7 days postinjury. Immunoblotting for phospho-IkappaBalpha demonstrated increased levels 1 day postinjury that remained elevated for at least 7 days. These data suggest that NF-kappaB signal transduction is involved in an adaptive response of neurons that survive injury.
Pennypacker
K R
KR
Department of Pharmacology and Therapeutics, University of South Florida, Tampa, Florida 33612, USA. kpennypa@hsc.usf.edu
Kassed
C A
CA
Eidizadeh
S
S
Saporta
S
S
Sanberg
P R
PR
Willing
A E
AE
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D002470:Cell Survival; D002536:Cerebral Arteries; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D006651:Histocytochemistry; D051550:I-kappa B Kinase; D015151:Immunoblotting; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009930:Organic Chemicals; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014298:Trimethyltin Compounds / Q000494:pharmacology
D005452:Fluoresceins; D005456:Fluorescent Dyes; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009930:Organic Chemicals; D014298:Trimethyltin Compounds; C435731:fluoro jade; C046488:trimethyltin; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase