Proteomic Profiling of Quercetin Growth Inhibitory Effect on Activated Hepatic Stellate Cells
| Autor: | Ying-Wei Lu, 呂穎維 |
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| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 In recent years, hepatic fibrosis is an important issue, due to progression of becoming hepatocellular carcinoma and liver cirrhosis in Taiwan. Activated hepatic stellate cells (HSCs) have been established as the unequivocal source of extracellular matrix in liver injury, regardless of the underlying disease. Hepatic stellate cells are quiescent and contain abundant of vitamin A, they will not proliferate or deposit protein unless liver damage occurs, which is referred as fibrogenesis. With continuous progress in human proteomic technology, it is possible to reveal protein profile for HSC. However, Quercetin is a flavanoid that serves as the backbone for many other flavanoids. It is consistently the most active of the flavanoids in experimental studies, and many medicinal plants owe much of their activity to their high quercetin content. Due to its antioxidant effect, quercetin has therapeutic potential in anti-inflammatory, anti-allergy, anti- ulcer, anti- cardiovascular disease and anti-cancer. In this study, two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrom- etry were employed to analyze the proteome of hepatic stellate cells treated with dose-dependent quercetin. Up-regulated or down-regulated proteins were analyzed by software, Imagemaster 2D Platinum. The comparison between such maps showed up- and down-regulation of 54 polypeptide chains, out of a total of 512 spots. Fingerprinting by MALDI-TOF mass spectrometry analysis enabled the identification of 16 of these spots. Among these proteins, of particular interest are the two-downregulated proteins α-enolase and vimentin, as well as the upregulated proteins peroxiredoxin 5, NFκB inhibitor-like protein. The modulation of these four proteins and the western bot of p53 and cyclin D1 are consistent with our observation that quercetin is able to inhibit cell growth of HSCs causing cell cycle arrest at the G1 phase and apoptotic cell death. These results demonstrated the growth inhibitory effect of quercetin on activated hepatic stellate cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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