碩士 / 國立陽明大學 / 神經科學研究所 / 95 / Brain is a cholesterol-rich organ and syntheses cholesterol. More and more studies have indicated that statin has positive effect to the disease of central nervous system. Hence many researchers devote into studying the pharmacologic mechanism of statins in neuronal cells. Cholesterol is an important component of cell membrane. However, statins inhibit the cholesterol synthesis in the cells. By loweringing the cholesterol content of the cells, statins may also change the membrane structure. In addition, statins also reduce the metabolic intermediates, the isorenoids, of the cholesterol synthetic pathway. Isoprenoid metabolites may participate in the post-translational modification of certain proteins, especially small GTPases. By isoprenylation, these proteins are able to insert on cell membrane. In summary, statins can change membranous small GTPase amount in two ways: one is to alter membrane structure, the other is to inhibit protein isoprenylation. The aim of this thesis is to study the underlying mechanisms of decreasing the membranous Rac in hippocampal astrocytes by lovastatin. Results of mevalonate supplement experiment indicated that the lovastatin effect was mediated by inhibiting HMG-CoA reductase. The results of GGPP supplement experiment also indicated that inhibition of protein isoprenylation also contributed to part of the mechanism of lovastatin. However, the partial effect of GGPP supplement experiments indicated other mechanisms might work. It is also possible that statins decrease membranous Rac1 by altering membrane structure at the same time.
| Identifer | oai:union.ndltd.org:TW/095YM005291011 |
| Date | January 2007 |
| Creators | Hsiang-Fan Cheng, 鄭向帆 |
| 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 | 55 |
Page generated in 0.017 seconds