Referenced in: none

Automatically associated channels: Kir4.1

Title: p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage.

Authors: Jun-hao Yan, Nikan H Khatibi, Hong-bin Han, Qin Hu, Chun-hua Chen, Li Li, Xiao-mei Yang, Chang-man Zhou

Journal, date & volume: CNS Neurosci Ther, 2012 Apr , 18, 334-42

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22420318

Abstract
To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH).We explored the role of aquaporin-4 (AQP4), inwardly rectifying K(+) 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin-α (PFT-α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT-α groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used.MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated-p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT-α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells.These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feet orchestrated by p38MAPK was partly responsible.