Cellular defense and metabolism are important biological processes in living cells. In this study, these two biological processes were investigated in two selected disease models: diabetes mellitus (DM) and severe acute respiratory syndrome associated coronavirus (SARS-CoV) infection by two-dimensional gel electrophoresis (2DE) coupled with Matrix-Assisted Laser Desorption Ionisation Time-Of-Flight Mass Spectrometry (MALDI-TOF MS)-based proteomic approaches. The major findings are summarized as follows: / Our results on DM investigation can help to better understand the pathophysiological changes in patients with DM and the pathogenesis of hyperglycemia-caused complications. Data obtained from SARS-CoV studies provided novel insights into the molecular basis of the host cell response upon viral infection. / Protein profile of streptozotocin (STZ)-induced diabetic animal tissues, including mice liver, kidney and eye, and rats sera, indicated that DM has an impaired cellular defense system. These include the impairment in reactive oxygen species scavenging and the impairment in activation of complement system and innate immunity, and the enhancement in blood coagulation reaction. Our results also demonstrated that glycolysis and gluconeogenesis did not alter significantly in the liver of STZ-diabetic mice, while fatty acid oxidation and TCA cycle were attenuated under the same conditions. Moreover, we also detected other abnormal metabolism in aldehyde and amino acid, especially glutamate metabolism and the urea cycle. Abnormalities were also detected in lipid transport and metabolism. Besides, protein profile of mouse liver c37 cells indicated that high glucose may induce apoptosis in these cells, and this apoptotic effect may be mediated via the mitochondrial pathway. Furthermore, the proteomic results from the in vivo and in vitro diabetic models have prompted us to look for glucose responsive element on the promoters of these up-regulated hepatic genes. We found that the mouse aldolase 2 gene has glucose responsiveness in c37 cells treated with high glucose by semi-quantitative RT-PCR and promoter transfection assay. Finally, protein profile of Vero E6 cells strongly implicated that SARS-CoV can induce anti-apoptosis. This effect may be mediated via the mitochondrial pathway. Our data also suggested that the anti-apoptotic activity may be required for viral replication at the early stage of infection. While under the condition of long-term infection, this may be needed for viral survival. / Zhong Mingqi. / "October 2005." / Advisers: Sai Ming Ngai; Hon Ki Cheng. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6217. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 223-248). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_343737 |
| Date | January 2005 |
| Contributors | Zhong, Mingqi., Chinese University of Hong Kong Graduate School. Division of Molecular Biotechnology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xix, 248 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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