Analysis of progressive changes in the protein N-linked glycosylation profile of mouse liver during the course of Schistosoma mansoni infection
Autor: | Ciou-Ping Lai, 賴秋萍 |
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Rok vydání: | 2004 |
Druh dokumentu: | 學位論文 ; thesis |
Popis: | 92 Schistosomiasis is a helminthic parasitic disease caused by blood flukes of the genus Schistosoma, afflicting about 200 million individuals in the tropics. The pathology of the disease is associated with egg deposition in the liver and intestines and is characterized by the formation of granulomas developing around viable egg, and become surrounded by leukocytes. In this work, mass spectrometry(MS)- based methodologies are employed to map the changes in the glycosylation profile of the liver tissue as a consequence of parasitic infection. Glycoproteins were extracted from liver of BALB/c mice infected with Schistosoma manson during a 18-week infectious cycle, which includes early stage, acute stage, and chronic stage. N-glycans were released, chemically derivatized, sequential exoglycosidase digested and subjected to MS mapping and MS/MS sequencing. The results show that there is a drastic change in the glycomic map as the normal liver developed into granuloma. There was a significant increase in the proportion of complex type glycan relative to high mansone type. Importantly, the sialylation pattern was changed from one that was mainly N- glycolylneuraminic acid(NeuGc) to one that was dominated by N- acetylylneuraminic acid (NeuAc). This change in the amount of N-glycan substituted with NeuGc or NeuAc was shown by RT-PCR to be a consequence of drcreased expression of a hydroxylase converting CMP- NeuAc into CMP- NeuGc. This model of a liver infection suggests that the protein N-glycosylation profile of mouse liver is characterized by a dynamic sialylation process being modulated by the altered expression of a specific enzyme during parasitic infection. |
Databáze: | Networked Digital Library of Theses & Dissertations |
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