RGD Reference Report - The role of PARL and HtrA2 in striatal neuronal injury after transient global cerebral ischemia. - Rat Genome Database

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The role of PARL and HtrA2 in striatal neuronal injury after transient global cerebral ischemia.

Authors: Yoshioka, Hideyuki  Katsu, Masataka  Sakata, Hiroyuki  Okami, Nobuya  Wakai, Takuma  Kinouchi, Hiroyuki  Chan, Pak H 
Citation: Yoshioka H, etal., J Cereb Blood Flow Metab. 2013 Nov;33(11):1658-65. doi: 10.1038/jcbfm.2013.139. Epub 2013 Aug 7.
RGD ID: 12902620
Pubmed: PMID:23921894   (View Abstract at PubMed)
PMCID: PMC3824183   (View Article at PubMed Central)
DOI: DOI:10.1038/jcbfm.2013.139   (Journal Full-text)

The presenilin-associated rhomboid-like (PARL) protein and high temperature requirement factor A2 (HtrA2) are key regulators of mitochondrial integrity and play pivotal roles in apoptosis. However, their roles after cerebral ischemia have not been thoroughly elucidated. To clarify these roles, mice were subjected to transient global cerebral ischemia, and striatal neuronal injury was assessed. Western blot and coimmunoprecipitation analyses revealed that PARL and processed HtrA2 localized to mitochondria, and that PARL was bound to HtrA2 in sham animals. Expression of PARL and processed HtrA2 in mitochondria significantly decreased 6 to 72¿hours after ischemia, and the binding of PARL to HtrA2 disappeared after ischemia. In contrast, expression of processed HtrA2 increased 24¿hours after ischemia in the cytosol, where HtrA2 was bound to X chromosome-linked inhibitor-of-apoptosis protein (XIAP). Administration of PARL small interfering RNA inhibited HtrA2 processing and worsened ischemic neuronal injury. Our results show that downregulation of PARL after ischemia is a key step in ischemic neuronal injury, and that it decreases HtrA2 processing and increases neuronal vulnerability. In addition, processed HtrA2 released into the cytosol after ischemia contributes to neuronal injury via inhibition of XIAP.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PARLHumantransient cerebral ischemia severityISOParl (Mus musculus) RGD 
ParlRattransient cerebral ischemia severityISOParl (Mus musculus) RGD 
ParlMousetransient cerebral ischemia severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Parl  (presenilin associated, rhomboid-like)

Genes (Mus musculus)
Parl  (presenilin associated, rhomboid-like)

Genes (Homo sapiens)
PARL  (presenilin associated rhomboid like)


Additional Information