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学科主题: 基础医学
题名:
p53-Induced Uncoupling Expression of Aquaporin-4 and Inwardly Rectifying K+ 4.1 Channels in Cytotoxic Edema after Subarachnoid Hemorrhage
作者: Yan, Jun-hao1,2; Khatibi, Nikan H.3; Han, Hong-bin4; Hu, Qin2; Chen, Chun-hua1,2; Li, Li1; Yang, Xiao-mei1; Zhou, Chang-man1
关键词: Astrocyte ; Cytotoxic edema ; p53 ; Rat ; Subarachnoid hemorrhage
刊名: CNS NEUROSCIENCE & THERAPEUTICS
发表日期: 2012
DOI: 10.1111/j.1755-5949.2012.00299.x
卷: 18, 期:4, 页:334-342
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences ; Pharmacology & Pharmacy
研究领域[WOS]: Neurosciences & Neurology ; Pharmacology & Pharmacy
关键词[WOS]: EARLY BRAIN-INJURY ; CEREBRAL-ISCHEMIA ; PIFITHRIN-ALPHA ; RAT MODEL ; P53 ; ACTIVATION ; ASTROCYTES ; VASOSPASM ; APOPTOSIS ; MICE
英文摘要:

Aims: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH). 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-a (PFT-a) 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-a groups. At 24 h after SAH, MRI (diffusion-weighted imaging [DWI]), immunohistochemistry, and Western blot were used. Results: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT-a 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-a treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated-p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells. 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 feets orchestrated by p38MAPK was partly responsible.

语种: 英语
所属项目编号: 30901548 ; 30971527
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000302355000009
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52888
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Loma Linda Univ, Med Ctr, Dept Anesthesiol, Loma Linda, CA USA
2.Peking Univ, Dept Anat & Embryol, Sch Basic Med Sci, Beijing 100191, Peoples R China
3.Loma Linda Univ, Med Ctr, Dept Physiol & Pharmacol, Loma Linda, CA USA
4.Peking Univ, Dept Radiol, Hosp 3, Beijing 100191, Peoples R China

Recommended Citation:
Yan, Jun-hao,Khatibi, Nikan H.,Han, Hong-bin,et al. p53-Induced Uncoupling Expression of Aquaporin-4 and Inwardly Rectifying K+ 4.1 Channels in Cytotoxic Edema after Subarachnoid Hemorrhage[J]. CNS NEUROSCIENCE & THERAPEUTICS,2012,18(4):334-342.
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