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KMID : 0379520040200030179
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한국독성학회지
2004 Volume.20 No. 3 p.179 ~ p.185
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Overview on Molecular Toxicological Aspects of Helicobacter pylori Virulence Factor, Cytotoxin-associated Antigen A (CagA)
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Kim Byung-J.
Jung Hwa-Jin
Hwang Jee-Na
Kang Seok-Ha
Oh Se-Jin
Seo Young-Rok
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Abstract
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Helicobacter pylori (H. pylori) infects more than half of the people in the world as a major microbe to cause most of gastric diseases. Recently, cytotoxin associated-antigen A (CagA) is believed as one of the most important virulence factors of H. pylori. Molecular toxicological pathway of CagA is necessary to investigate for understanding the pathological and toxicological aspects of H. pylori, since this virulence protein harasses intercellular processes of host cells to get profit for the survival of H. pylori. CagA is coded from cag pathogenicity island (cag PAI) and translocated into host cells by Type 4 secretion system (TFSS). Tyrosine phosphorylation of CagA targets Src homology 2-containing phosphotyrosine phosphatase (SHP-2) to form a CagA-SHP-2 complex. This complex depends on the similarity of sequence between EPIYA motif and Src homology 2 domain (SH2 domain) of CagA. The generation of growth factors is an essential role of CagA in protecting and healing gastric mucosa for the survival of H. pylori. On the other hand, the activation of IL-8 by CagA induces neutrophils generating inflammation and free radicals. Indeed, free radicals are well known carcinogen to induce DNA damage. In addition, the transduction of mitogen-activation signal by CagA is one of the interesting features to understand how to cause cancer. The relationship between cancer and inflammation with CagA was mainly discussed in this review.
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KEYWORD
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CagA, Helicobactor pylori, ROS, IL-8, SHP-2, MAPK
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