RGD Reference Report - Evidence for the involvement of Par-4 in ischemic neuron cell death. - Rat Genome Database
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Evidence for the involvement of Par-4 in ischemic neuron cell death.

Authors: Culmsee, C  Zhu, Y  Krieglstein, J  Mattson, MP 
Citation: Culmsee C, etal., J Cereb Blood Flow Metab. 2001 Apr;21(4):334-43.
RGD ID: 9835381
Pubmed: (View Article at PubMed) PMID:11323519
DOI: Full-text: DOI:10.1097/00004647-200104000-00002

After a stroke many neurons in the ischemic brain tissue die by a process called apoptosis, a form of cell death that may be preventable. The specific molecular cascades that mediate ischemic neuronal death are not well understood. The authors recently identified prostate apoptosis response-4 (Par-4) as a protein that participates in the death of cultured hippocampal neurons induced by trophic factor withdrawal and exposure to glutamate. Here, the authors show that Par-4 levels increase in vulnerable populations of hippocampal and striatal neurons in rats after transient forebrain ischemia; Par-4 levels increased within 6 hours of reperfusion and remained elevated in neurons undergoing apoptosis 3 days later. After transient focal ischemia in mice, Par-4 levels were increased 6 to 12 hours after reperfusion in the infarcted cortex and the striatum, and activation of caspase-8 occurred with a similar time course. Par-4 immunoreactivity was localized predominantly in cortical neurons at the border of the infarct area. A Par-4 antisense oligonucleotide protected cultured hippocampal neurons against apoptosis induced by chemical hypoxia and significantly reduced focal ischemic damage in mice. The current data suggest that early up-regulation of Par-4 plays a pivotal role in ischemic neuronal death in animal models of stroke and cardiac arrest.

Annotation

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Pawr  (pro-apoptotic WT1 regulator)

Genes (Mus musculus)
Pawr  (PRKC, apoptosis, WT1, regulator)

Genes (Homo sapiens)
PAWR  (pro-apoptotic WT1 regulator)


Additional Information