Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Zhong Fang Shi; Wei Jiang Zhao; Li Xin XU; Li Ping Dong; Shao Hua Yang; Fang Yuan

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Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Author: Zhong Fang SHI ^{1
,

2} ; Wei Jiang ZHAO ³ ; Li Xin XU ¹ ; Li Ping DONG ¹ ; Shao Hua YANG ¹ ; Fang YUAN ¹ ;
Author Information

1. Department of Pathophysiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
2. Beijing Key Laboratory of Central Nervous System Injury, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China.
3. Center for Neuroscience, Shantou University Medical College, Shantou 515041, Guangdong, China.
Publication Type:Journal Article
Keywords: Aquaporin 4; Astrocytes; Extracellular signal-regulated kinases1/2; Scratch-injury
MeSH: Animals; Aquaporin 4; metabolism; Astrocytes; enzymology; metabolism; Butadienes; administration & dosage; Cells, Cultured; Down-Regulation; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; metabolism; MAP Kinase Signaling System; Nitriles; administration & dosage; Rats; Rats, Wistar; Skin; injuries
From: Biomedical and Environmental Sciences 2015;28(3):199-205
CountryChina
Language:English
Abstract:
OBJECTIVETo investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.
METHODSThe scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.
RESULTSIncreases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.
CONCLUSIONThese results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.