RGD Reference Report - Distinct patterns of intracerebral hemorrhage-induced alterations in NF-kappaB subunit, iNOS, and COX-2 expression. - Rat Genome Database

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Distinct patterns of intracerebral hemorrhage-induced alterations in NF-kappaB subunit, iNOS, and COX-2 expression.

Authors: Zhao, X  Zhang, Y  Strong, R  Zhang, J  Grotta, JC  Aronowski, J 
Citation: Zhao X, etal., J Neurochem. 2007 May;101(3):652-63. Epub 2007 Jan 23.
RGD ID: 2302394
Pubmed: PMID:17250675   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2006.04414.x   (Journal Full-text)

Transcription factor nuclear factor-kappaB (NF-kappaB), plays a key role in regulating inflammation in brain pathologies. The goal of this study was to characterize temporal changes in NF-kappaB activation, NF-kappaB subunit expression, and expression of selected NF-kappaB-regulated gene products [inducible form of nitric oxide synthase (iNOS) and cyclooxygenase-2], at the transcriptional and translational level in the brain after intracerebral hemorrhage (ICH). Employing the intrastriatal injection of autologous blood in rats to model ICH, we demonstrated, using NF-kappaB-DNA binding assay, a robust and prolonged NF-kappaB activation, starting as early as 15 min after the onset of ICH. Consequently, we demonstrated that the mRNA and protein for p50, p52, p65, c-Rel, and RelB NF-kappaB subunits, as well as IkappaBalpha were all up-regulated, with a time course ranging from minutes to days following ICH, depending on the subunit. Using reverse transcription-polymerase chain reaction to analyze mRNA and immunoblotting to analyze protein in ICH-affected tissue, we found robust induction of iNOS at both mRNA and protein levels that followed a time-course similar to changes in p65, p52, and RelB mRNA. Oddly, in contrast to iNOS, cyclooxygenase-2 mRNA and protein following an early transient increase demonstrated significant reduction in response to ICH. In summary, NF-kappaB activation occurs within minutes and persists for at least a week in response to ICH. This reaction utilizes different NF-kappaB regulatory subunits and is associated with the expression of selected target genes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cerebral Hemorrhage  ISONfkb1 (Rattus norvegicus)2302394; 2302394protein:increased activity:striatumRGD 
Cerebral Hemorrhage  ISONfkb2 (Rattus norvegicus)2302394; 2302394protein:increased activity:striatumRGD 
Cerebral Hemorrhage  IDA 2302394; 2302394; 2302394protein:increased activity:striatumRGD 
Cerebral Hemorrhage  ISORela (Rattus norvegicus)2302394; 2302394protein:increased activity:striatumRGD 
Cerebral Hemorrhage  ISORelb (Rattus norvegicus)2302394; 2302394mRNA more ...RGD 
Cerebral Hemorrhage  IDA 2302394mRNA more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA binding  IDA 2302394 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfkb1  (nuclear factor kappa B subunit 1)
Nfkb2  (nuclear factor kappa B subunit 2)
Rela  (RELA proto-oncogene, NF-kB subunit)
Relb  (RELB proto-oncogene, NF-kB subunit)

Genes (Mus musculus)
Nfkb1  (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105)
Nfkb2  (nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100)
Rela  (v-rel reticuloendotheliosis viral oncogene homolog A (avian))
Relb  (avian reticuloendotheliosis viral (v-rel) oncogene related B)

Genes (Homo sapiens)
NFKB1  (nuclear factor kappa B subunit 1)
NFKB2  (nuclear factor kappa B subunit 2)
RELA  (RELA proto-oncogene, NF-kB subunit)
RELB  (RELB proto-oncogene, NF-kB subunit)


Additional Information