RGD Reference Report - Excessive autophagy contributes to neuron death in cerebral ischemia. - Rat Genome Database

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Excessive autophagy contributes to neuron death in cerebral ischemia.

Authors: Shi, R  Weng, J  Zhao, L  Li, XM  Gao, TM  Kong, J 
Citation: Shi R, etal., CNS Neurosci Ther. 2012 Mar;18(3):250-60. doi: 10.1111/j.1755-5949.2012.00295.x.
RGD ID: 6483050
Pubmed: PMID:22449108   (View Abstract at PubMed)
PMCID: PMC6493486   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1755-5949.2012.00295.x   (Journal Full-text)

AIMS: To determine the extent to which autophagy contributes to neuronal death in cerebral hypoxia and ischemia. METHODS: We performed immunocytochemistry, western blot, cell viability assay, and electron microscopy to analyze autophagy activities in vitro and in vivo. RESULTS: In both primary cortical neurons and SH-SY5Y cells exposed to oxygen and glucose deprivation (OGD)for 6 h and reperfusion (RP) for 24, 48, and 72 h, respectively, an increase of autophagy was observed as determined by the increased ratio of LC3-II to LC3-I and Beclin-1 (BECN1) expression. Using Fluoro-Jade C and monodansylcadaverine double-staining, and electron microscopy we found the increment in autophagy after OGD/RP was accompanied by increased autophagic cell death, and this increased cell death was inhibited by the specific autophagy inhibitor, 3-methyladenine. The presence of large autolysosomes and numerous autophagosomes in cortical neurons were confirmed by electron microscopy. Autophagy activities were increased dramatically in the ischemic brains 3-7 days postinjury from a rat model of neonatal cerebral hypoxia/ischemia as shown by increased punctate LC3 staining and BECN1 expression. CONCLUSION: Excessive activation of autophagy contributes to neuronal death in cerebral ischemia.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BECN1HumanBrain Hypoxia-Ischemia  ISOBecn1 (Rattus norvegicus)protein:increased expression:cerebral cortexRGD 
Becn1RatBrain Hypoxia-Ischemia  IEP protein:increased expression:cerebral cortexRGD 
Becn1MouseBrain Hypoxia-Ischemia  ISOBecn1 (Rattus norvegicus)protein:increased expression:cerebral cortexRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Becn1Ratresponse to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Becn1  (beclin 1)

Genes (Mus musculus)
Becn1  (beclin 1, autophagy related)

Genes (Homo sapiens)
BECN1  (beclin 1)


Additional Information