RGD Reference Report - Activated mitogen-activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N-terminal kinase-interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region. - Rat Genome Database

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Activated mitogen-activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N-terminal kinase-interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region.

Authors: Li, CH  Wang, RM  Zhang, QG  Zhang, GY 
Citation: Li CH, etal., J Neurochem. 2005 Apr;93(2):290-8.
RGD ID: 1579811
Pubmed: PMID:15816852   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2005.03086.x   (Journal Full-text)

Mitogen-activated protein kinase kinase (MKK) 7, a specific upstream activator of Jun N-terminal kinases (JNKs) in the stress-activated protein kinase (SAPK)/JNK signaling pathway, plays an important role in response to global cerebral ischemia. We investigated the subcellular localization of activated (phosphorylated) MKK (p-MKK) 7 using western blotting, immunoprecipitation and immunohistochemistry analysis in rat hippocampus. Transient forebrain ischemia was induced by the four-vessel occlusion method on Sprague-Dawley rats. Our results showed that both protein expression and activation of MKK7 were increased rapidly with peaks at 10 min of reperfusion in the nucleus of the hippocampal CA1 region. Simultaneously, in the cytosol activated MKK7 enhanced gradually and peaked at 30 min of reperfusion. In addition, we also detected JNK-interacting protein (JIP) 1, which accumulated in the perinuclear region of neurons at 30 min of reperfusion. Interestingly, at the same time-point the binding of JIP-1 to p-MKK7 reached a maximum. Consequently, we concluded that MKK7 was rapidly activated and then translocated from the nucleus to the cytosol depending on its activation in the hippocampal CA1 region. To further elucidate the possible mechanism of MKK7 activation and translocation, the antioxidant N-acetylcysteine was injected into the rats 20 min before ischemia. The result showed that the levels of MKK7 activation, translocation and binding of p-MKK7 to JIP-1 were obviously limited by N-acetylcysteine in the cytosol at 30 min after reperfusion. The findings suggested that MKK7 activation, translocation and binding to JIP-1 were closely associated with reactive oxygen species and might play a pivotal role in the activation of the JNK signaling pathway in brain ischemic injury.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
perinuclear region of cytoplasm  IDA 1579811 RGD 

Molecular Function

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Map2k7  (mitogen activated protein kinase kinase 7)
Mapk8ip1  (mitogen-activated protein kinase 8 interacting protein 1)

Genes (Mus musculus)
Mapk8ip1  (mitogen-activated protein kinase 8 interacting protein 1)

Genes (Homo sapiens)
MAPK8IP1  (mitogen-activated protein kinase 8 interacting protein 1)


Additional Information