RGD Reference Report - Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro. - Rat Genome Database

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Interleukin-1 receptor associated kinases-1/4 inhibition protects against acute hypoxia/ischemia-induced neuronal injury in vivo and in vitro.

Authors: Yang, YF  Chen, Z  Hu, SL  Hu, J  Li, B  Li, JT  Wei, LJ  Qian, ZM  Lin, JK  Feng, H  Zhu, G 
Citation: Yang YF, etal., Neuroscience. 2011 Nov 24;196:25-34. doi: 10.1016/j.neuroscience.2011.08.059. Epub 2011 Sep 10.
RGD ID: 7495802
Pubmed: PMID:21925238   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2011.08.059   (Journal Full-text)

Neuronal Toll-like receptors (TLRs)-2 and -4 have been shown to play a pivotal role in ischemic brain injury, and the interleukin-1 receptor associated kinases (IRAKs) are considered to be the key signaling molecules involved downstream of TLRs. Here, we investigated the expression levels of IRAK-1 and -4 and the effects of IRAK-1/4 inhibition on brain ischemic insult and neuronal hypoxia-induced injury. Male Sprague-Dawley (SD) rats and the rat neuroblastoma B35 cell line were used in these experiments. Permanent middle cerebral artery occlusion (MCAO) was induced by the intraluminal filament technique, and B35 cells were stimulated with the hypoxia-mimetic, cobalt chloride (CoCl(2)). Following induction of hypoxia/ischemia (H/I), B35 cells and cerebral cortical neurons expressed higher levels of IRAK-1 and -4. Furthermore, IRAK-1/4 inhibition decreased the mortality rate, functional deficits, and ischemic infarct volume by 7 days after MCAO. Similarly, IRAK-1/4 inhibition attenuated CoCl(2)-induced cytotoxicity and apoptosis in B35 cells in vitro. Our results show that IRAK-1/4 inhibition decreased the nuclear translocation of the nuclear factor-kappaB (NF-kappaB) p65 subunit, the levels of activated (phosphorylated) c-jun N-terminal kinase (JNK) and cleaved caspase-3, and the secretion of TNF-alpha and IL-6 in B35 cells at 6 h after CoCl(2) treatment. These data suggest that IRAK-1/4 inhibition plays a neuroprotective role in H/I-induced brain injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain ischemia  ISOIrak1 (Rattus norvegicus)7495802; 7495802mRNA and protein:increased expression:cerebral cortexRGD 
brain ischemia  ISOIrak4 (Rattus norvegicus)7495802; 7495802mRNA and protein:increased expression:cerebral cortexRGD 
brain ischemia  IEP 7495802; 7495802mRNA and protein:increased expression:cerebral cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Irak1  (interleukin-1 receptor-associated kinase 1)
Irak4  (interleukin-1 receptor-associated kinase 4)

Genes (Mus musculus)
Irak1  (interleukin-1 receptor-associated kinase 1)
Irak4  (interleukin-1 receptor-associated kinase 4)

Genes (Homo sapiens)
IRAK1  (interleukin 1 receptor associated kinase 1)
IRAK4  (interleukin 1 receptor associated kinase 4)


Additional Information