Project/Area Number |
09557050
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Gastroenterology
|
Research Institution | Jichi Medical School (1998-1999) The University of Tokyo (1997) |
Principal Investigator |
SUGANO Kentaro Jichi Med. Sch., Faculty Medicine, Professor, 医学部, 教授 (60179116)
|
Co-Investigator(Kenkyū-buntansha) |
SATO Yukihiro Jichi Med. Sch., Faculty Medicine, Research Assistant, 医学部, 助手
SATOH Kiichi Jichi Med. Sch., Faculty Medicine, Lecturer, 医学部, 講師 (50275707)
OSAWA Hiroyuki Jichi Med. Sch., Faculty Medicine, Research Assistant, 医学部, 助手 (70260833)
福嶋 康之 東京大学, 医学部・附属病院・消化器内科, 医員
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥7,400,000 (Direct Cost: ¥7,400,000)
|
Keywords | Helicobacter pylori / adhesin / sulfatide / Helicobacter pylori / 接着 / ヘリコバクターピロリ / 糖脂質 |
Research Abstract |
Attachment of Helicobacter pylon (HP) to gastric epithelium is a crucial step for perpetuating the infection. Tight adhesion of the organism to the epithelium profoundly affects the epithelial function causing various diseases. The attachment is mediated by specific bacterial proteins called adhesins which recognize specific receptors. In most cases, cell surface glycoconjugates have been demonstrated as bacterial adhesion receptors. In the case of HP, several putative adhesins with different receptor specificities have been reported. In this project, we tried to identify adhesins which specifically recognize sulfatide. Using two different affimty chromatographies, one with heparin-sepharose and the other with sulfated cellulose, two candidate proteins from sonicated supernatant from HP were identified. Several partial amino acid sequences of the peptides derived from affinity-purified proteins were obtained By searching homologous sequences in the genome data of HP, one was identified as heat shock protein 60 (HSP) and the other as a functionally unknown protein. Since other researchers hypothesized HSP as a putative adhesin acting at the initial step of bacterial attachment, we cloned HSP gene to clarify the binding specificity of HSP. This work is now in progress. Secondary, we tried to characterize the adhesion receptors in Mongolian gerbils which have been known as a suitable animal model of human gastric ulcer and cancer induced by HP infection. In this animal, sulfatides were abundantly expressed in the gastric mucosa compared with mice, indicating the higher number of bacterial attachment seen in this animal may be due to receptor abundance. This result is now submitted for publication. To further confirm the role of sulfatide as a receptor, we have cloned human sulfotransferase. The expression of sulfotransferase in the sulfatide-deficient cells is now in progress.
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