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p53-induced uncoupling expression of aquaporin-4 and inwardly rectifying K+ 4.1 channels in cytotoxic edema after subarachnoid hemorrhage.
- Source :
-
CNS neuroscience & therapeutics [CNS Neurosci Ther] 2012 Apr; Vol. 18 (4), pp. 334-42. Date of Electronic Publication: 2012 Mar 15. - Publication Year :
- 2012
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Abstract
- Aims: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH).<br />Methods: 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.<br />Results: 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.<br />Conclusion: 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.<br /> (© 2012 Blackwell Publishing Ltd.)
- Subjects :
- Animals
Benzothiazoles pharmacology
Brain Edema complications
Gene Expression Regulation
Hippocampus metabolism
Male
Potassium Channels, Inwardly Rectifying genetics
Rats
Rats, Sprague-Dawley
Subarachnoid Hemorrhage complications
Toluene analogs & derivatives
Toluene pharmacology
Tumor Suppressor Protein p53 genetics
Aquaporin 4 biosynthesis
Brain Edema metabolism
Potassium Channels, Inwardly Rectifying biosynthesis
Subarachnoid Hemorrhage metabolism
Tumor Suppressor Protein p53 antagonists & inhibitors
Tumor Suppressor Protein p53 biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1755-5949
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- CNS neuroscience & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 22420318
- Full Text :
- https://doi.org/10.1111/j.1755-5949.2012.00299.x