Helicobacter pylori (H. pylori) causes peptic ulcer or gastric cancer through different virulence factors including lipopolysaccharides (LPS), the cytotoxin-associated gene A product (CagA), and vacuolating
cytotoxin A (VacA) etc. It stimulated mitogen-activated protein (MAP) kinase signaling cascades. Small ubiquitin-related modifier (SUMO) is a member of ubiquitin-related protein modifiers. However, the mechanisms of the involvement of SUMO-1 on H. pylori induced apoptosis were not clear. Our previous study showed that the expression of RFP-SUMO-1
and apoptosis were increased significantly by fluorescence microscopy assays on RFP-SUMO-1 transfectants during H. pylori infection. In addition, the cytoplasmic SUMO-1 was increased during infection and positively associated with apoptosis. Here, how SUMO-1 was involved in the apoptotic signaling enhancement during H. pylori infection was
studied. Results showed that H. pylori infection enhanced MAP kinase activation and the effects were stronger on the SUMO-1 overexpressed cells. However, it was not affected by the secretion of CagA or VacA toxins of H. pylori. To investigate the possible role of SUMO-1 on MAPKs mediated signaling pathways, three selective MAPKs inhibitors were used on RFP-SUMO-1 overexpressed cells. Only p38 inhibitor decreased the levels of apoptosis during H. pylori infection and the expression of p53 was increased on RFP-SUMO-1 1 overexpressed cells.
Thus, p38 and p53 pathways were suggested to be involved in SUMO-1 enhanced apoptosis during H. pylori infection. In addition, the nuclear localization of NF-£eB and expression of COX-2 were enhanced on
RFP-SUMO-1 overexpressed cells. Moreover, more nuclear NF-£eB and cytoplasmic as well as nuclear RFP-SUMO-1 were observed during H. pylori infection. Our data suggest that H. pylori infection enhances
SUMO-1 expression which activates MAPKs on both the pro-apoptotic p38-p53 pathway and the anti-apoptotic ERK-NF-£eB-COX2 pathway. The detail mechanisms on how cells making the final decision on the survival or apoptosis were still not clear and deserving to investigate.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0209108-114548 |
| Date | 09 February 2008 |
| Creators | Lin, Chia-hui |
| Contributors | Wen-chun Hung, Angela Chen, Teng-chiang Wu |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0209108-114548 |
| Rights | not_available, Copyright information available at source archive |
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