RGD Reference Report - Protective effect of Ginkgolids (A+B) is associated with inhibition of NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia.

Advanced Search (OLGA)

General

Protective effect of Ginkgolids (A+B) is associated with inhibition of NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia.
Authors:	Wang, X Qin, ZH Shi, H Savitz, SI Qin, AP Jiang, Y Zhang, HL
Citation:	Wang X, etal., Brain Res. 2008 Oct 9;1234:8-15. Epub 2008 Aug 5.
RGD ID:	2313425
Pubmed:	PMID:18722355 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.brainres.2008.07.102 (Journal Full-text)
BACKGROUND AND PURPOSE: We have previously reported that Ginkgolids which contain Ginkgolids A and B (Ginkgolids (A+B), GKAB) reduce infarct size in a rat model of focal ischemia. NF-kappaB-inducing kinase (NIK)-IkappaBalpha kinase (IKK) pathway plays an important role in activation of nuclear factor kappaB (NF-kappaB). A previous study demonstrated that Ginkgolid B inhibited lipopolysaccharide (LPS)- and platelet activating factor (PAF)-induced NF-kappaB activation in rat pleural polymorphonuclear granulocytes. However, little is known about the inhibitory mechanisms of Ginkgolids on the activation of NF-kappaB. The present study evaluated the effects of GKAB on NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. GKAB was injected intravenously (iv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in IkappaBalpha, phosphorylated NIK (p-NIK) and phosphorylated IKKalpha (p-IKKalpha). Immunohistochemistry was used to confirm the nuclear translocation of NF-kappaB p65. RT-PCR was used to detect induction of NF-kappaB target gene c-Myc mRNA. RESULTS: The results showed a brief increase in p-NIK levels after ischemia. GKAB blocked ischemia-induced increases in p-NIK and p-IKKalpha levels, and reversed the decline in IkappaBalpha levels. Ischemia-induced nuclear translocation of NF-kappaB p65 was attenuated by GKAB(.) GKAB also repressed the ischemia-induced increase in expression of NF-kappaB target gene c-Myc mRNA. CONCLUSIONS: These findings suggest that GKAB-mediated neuroprotective effect against ischemia appears to be associated with blocking NF-kappaB activation by suppressing the NIK-IKK pathway.

Annotation Click to see Annotation Detail View

Gene Ontology Annotations Click to see Annotation Detail View

Biological Process

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Map3k14	Rat	protein phosphorylation		IMP			RGD

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Map3k14	Rat	protein kinase activity		IMP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Map3k14 (mitogen-activated protein kinase kinase kinase 14)

Objects referenced in this article

Gene	Rela	RELA proto-oncogene, NF-kB subunit	Rattus norvegicus

Additional Information

Gene Annotator (Functional Annotation) unavailable	Gene Annotator (Annotation Distribution) unavailable	Variant Visualizer (Genomic Variants) unavailble Variant Visualizer (Genomic Variants) unavailable
Gene Annotator (Functional Annotation)	Gene Annotator (Annotation Distribution)	Variant Visualizer (Genomic Variants)

InterViewer (Protein-Protein Interactions) unavailable	Gviewer (Genome Viewer) unavailable	Variant Visualizer (Damaging Variants) unavailble Variant Visualizer (Damaging Variants) unavailable
InterViewer (Protein-Protein Interactions)	GViewer (Genome Viewer)	Variant Visualizer (Damaging Variants)

Gene Annotator (Annotation Comparison) unavailable	OLGA (Gene List Generator) unavailable
Gene Annotator (Annotation Comparison)	OLGA (Gene List Generator)	Excel (Download)

MOET (Multi-Ontology Enrichement) unavailable	GOLF (Gene-Ortholog Location Finder) unavailable
MOET (Multi-Ontology Enrichement)	GOLF (Gene-Ortholog Location Finder)

Create Name:

Description:

Send us a Message

Protective effect of Ginkgolids (A+B) is associated with inhibition of NIK/IKK/IkappaB/NF-kappaB signaling pathway in a rat model of permanent focal cerebral ischemia.