碩士 / 國立陽明大學 / 神經科學研究所 / 93 / Previous study demonstrated that cholesterol deficiency exacerbated glutamate (Glu)-induced cytotoxicity to hippocampal astrocytes, increased the phosphorylation of ERK1/2, and decreased the expression and activity of glutamine synthetase (GS). Moreover, morphological changes and disorganization of actin cytoskeleton were observed in astrocytes of cholesterol deficiency. This study was aimed to investigate the signaling pathways involved in the enhanced vulnerability of cholesterol-deficient astrocytes to Glu-induced cell death.
To find out the cause of actin changes, Rho GTPase protein, which is involved in regulation of actin cytoskeleton was studied. Cholesterol depletion by treating astrocytes with lovastatin and β-cyclodextrin increased the cytosolic while decreasing membranous expression of Rho and Rac-1. These results suggested that cholesterol depletion affected the activation of Rho GTPase protein which in turn caused actin structure changes. In addition, the results of immunocytochemical staining showed that the actin ring structures of cholesterol-deficient astrocytes were not restored after Glu stimulated and recovery period. These results suggested that the complete of actin cytoskeleton might play a role in cholesterol deprivation aggravating Glu-induced cell death.
Glu exposure did not modulate the inhibitory effect of cholesterol deprivation on GS expression. Glu caused rapid and transient increases in the phosphorylation of ERK1/2. The elevated level of phosphorylated ERK1/2 remained apparent in cholesterol-deficient astrocytes after Glu exposure. Immunocytochemical staining study revealed prominent increases in the nuclear expression of pERK1/2. These results suggested that the elevated level of phosphorylated ERK1/2 might involve in the enhanced vulnerability of cholesterol-deficient astrocytes to Glu-induced cell death.
| Identifer | oai:union.ndltd.org:TW/093YM005291008 |
| Date | January 2005 |
| Creators | Mei-Yun Chen, 陳美雲 |
| Contributors | Yun-Chia Chou, 周韻家 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 0 |
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