RGD Reference Report - Over-expression of map kinase phosphatase-1 (MKP-1) suppresses neuronal death through regulating JNK signaling in hypoxia/re-oxygenation. - Rat Genome Database

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Over-expression of map kinase phosphatase-1 (MKP-1) suppresses neuronal death through regulating JNK signaling in hypoxia/re-oxygenation.

Authors: Koga, S  Kojima, S  Kishimoto, T  Kuwabara, S  Yamaguchi, A 
Citation: Koga S, etal., Brain Res. 2012 Feb 3;1436:137-46. doi: 10.1016/j.brainres.2011.12.004. Epub 2011 Dec 8.
RGD ID: 7771582
Pubmed: PMID:22197701   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2011.12.004   (Journal Full-text)

A pivotal role of c-jun N-terminal kinase (JNK) on neuronal apoptosis has been demonstrated in a rodent stroke model. MAP kinase phosphatase 1 (MKP-1) is an archetypal member of the dual-specificity protein phosphatase (DUSP) family, which inactivates mitogen-activated protein kinase (MAPK) including JNK through dephosphorylation. MKP-1, one of immediate early genes in stress conditions, was induced at transcriptional level in hypoxia/re-oxygenation (H/R) in neuroblastoma N1E115 cells, however the activation of JNK was not suppressed in the acute phase of re-oxygenation. Small interference RNA-mediated knock-down of MKP-1 enhanced phospho-JNK and neuronal death that is rescued by JNK inhibitor in H/R. Conversely, conditional over-expression of MKP-1 suppressed phospho-JNK, the expression of proapoptotic genes, and neuronal death in H/R. Further the immunoreactivity of MKP-1 was detected in the neurons and partially co-localized with that of phospho-JNK in the surrounding zone of ischemia in rat MCA-O (middle cerebral artery occlusion) reperfusion model. These findings indicate that over-expression of MKP-1 could suppress neuronal death possibly through regulating JNK signaling in vitro and be a prominent neuroprotective target for the treatment of acute cerebral infarction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISODusp1 (Rattus norvegicus)7771582; 7771582protein:increased expression:brainRGD 
transient cerebral ischemia  IEP 7771582protein:increased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Dusp1  (dual specificity phosphatase 1)

Genes (Mus musculus)
Dusp1  (dual specificity phosphatase 1)

Genes (Homo sapiens)
DUSP1  (dual specificity phosphatase 1)


Additional Information