RGD Reference Report - Pinocembrin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress induced apoptosis. - Rat Genome Database
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Pinocembrin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress induced apoptosis.

Authors: Wu, CX  Liu, R  Gao, M  Zhao, G  Wu, S  Wu, CF  Du, GH 
Citation: Wu CX, etal., Neurosci Lett. 2013 Jun 24;546:57-62. doi: 10.1016/j.neulet.2013.04.060. Epub 2013 May 10.
RGD ID: 10395346
Pubmed: (View Article at PubMed) PMID:23669639
DOI: Full-text: DOI:10.1016/j.neulet.2013.04.060

Endoplasmic reticulum stress (ER stress) is known to play a vital role in mediating ischemic reperfusion damage in brain. Our previous studies showed that pinocembrin alleviated cerebral ischemic injury in ischemia/reperfusion and vascular dementia animal models, but whether attenuation of ER stress-induced apoptosis contributes to the mechanisms remains to be elucidated. In this study, an attempt was therefore made to investigate the modulation effect of pinocembrin on ischemia/reperfusion-induced ER stress in brain. Focal cerebral ischemia/reperfusion rats were induced by middle cerebral artery occlusion (MCAO) for 2h followed by 6h reperfusion. Pinocembrin was administered in different doses (1mg/kg, 3mg/kg, and 10mg/kg, respectively) at the same time of onset of reperfusion. Neurological function and brain infarction were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, and flow cytometer (FCM) were used to investigate cell apoptosis in penumbra cortex. DNA fragmentation assay was also performed using electrophoresis. The expression of ER stress proteins of GRP78, CHOP/GADD153, ATF4, eIF2alpha phosphorylation was detected by western blot, and caspase-12 was evaluated by immunohistochemical analysis. Our results demonstrate that pinocembrin-treatment (3mg/kg and 10mg/kg) significantly reduced neurological deficit scores, infarct volume, and neuron apoptosis in the ischemia/reperfusion rats. It can also significantly modulate the protein levels by increasing GRP78 (10mg/kg) and attenuating CHOP/GADD153 expression along with caspase-12 activation (3mg/kg and 10mg/kg). At the same time, eIF2alpha phosphorylation was restrained and the expression of ATF4 was reduced (3mg/kg and 10mg/kg). These results suggest that the attenuation of ER stress induced apoptosis may be involved in the mechanisms of pinocembrin.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Eif2s1  (eukaryotic translation initiation factor 2 subunit alpha)

Genes (Mus musculus)
Eif2s1  (eukaryotic translation initiation factor 2, subunit 1 alpha)

Genes (Homo sapiens)
EIF2S1  (eukaryotic translation initiation factor 2 subunit alpha)


Additional Information