RGD Reference Report - CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes. - Rat Genome Database

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CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes.

Authors: Qi, LL  Fang, SH  Shi, WZ  Huang, XQ  Zhang, XY  Lu, YB  Zhang, WP  Wei, EQ 
Citation: Qi LL, etal., Life Sci. 2011 Jan 3;88(1-2):50-6. Epub 2010 Nov 3.
RGD ID: 5144006
Pubmed: PMID:21055410   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2010.10.025   (Journal Full-text)

AIMS: We previously reported that cysteinyl leukotriene receptor 2 (CysLT(2)) mediates ischemic astrocyte injury, and leukotriene D(4)-activated CysLT(2) receptor up-regulates the water channel aquaporin 4 (AQP4). Here we investigated the mechanism underlying CysLT(2) receptor-mediated ischemic astrocyte injury induced by 4-h oxygen-glucose deprivation and 24-h recovery (OGD/R). MAIN METHODS: Primary cultures of rat astrocytes were treated by OGD/R to construct the cell injury model. AQP4 expression was inhibited by small interfering RNA (siRNA). The expressions of AQP4 and CysLTs receptors, and the MAPK signaling pathway were determined. KEY FINDINGS: OGD/R induced astrocyte injury, and increased expression of the CysLT(2) (but not CysLT(1)) receptor and AQP4. OGD/R-induced cell injury and AQP4 up-regulation were inhibited by a CysLT(2) receptor antagonist (Bay cysLT2) and a non-selective CysLT receptor antagonist (Bay u9773), but not by a CysLT(1) receptor antagonist (montelukast). Knockdown of AQP4 by siRNA attenuated OGD/R injury. Furthermore, OGD/R increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the cell injury and AQP4 up-regulation. SIGNIFICANCE: The CysLT(2) receptor mediates AQP4 up-regulation in astrocytes, and up-regulated AQP4 leads to OGD/R-induced injury, which results from activation of the ERK1/2 and p38 MAPK pathways.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of ERK1 and ERK2 cascade  IMP 5144006 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cysltr2  (cysteinyl leukotriene receptor 2)


Additional Information