Analysis of molecular mechanism of pathogenesis from disturbance of cell polarity caused by oxidative stress response
| Project/Area Number |
16K08739
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Research Collaborator |
Ohno Shigeo
Hirose Tomonori
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細胞極性 / 酸化ストレス / 炎症 / aPKC / 上皮細胞 |
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| Outline of Final Research Achievements |
Inflammatory bowel diseases processes disrupts the barrier function, inducing epithelial cell polarity. Increased permieability leads to oxidative stress-mediated chronic of inflammation. However, the effect of oxidative stress on epithelial polarity or epithelial morphology is unknown. We have also revealed that carbon tetrachloride (CCl4)-induced oxidative stress resulted in disassembly of TJs through aberrant activation of aPKC. In this study, we found that oxidative stress-mediated oxidized phosphatidylserine (OxPS) induced provokes a disturbance of epithelial cell polarity through aberrant activation of aPKC.
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| Academic Significance and Societal Importance of the Research Achievements |
炎症性病態では、酸化ストレスに暴露されており、抗酸化作用を持つ薬剤の投与で細胞障害を抑制できると想定されるが十分な効果は得られていない。その理由として酸化ストレスによる脂溶性情報伝達物質の過酸化体の生成と、その生理活性の変化が抗酸化による防御機構を上回るためと考えられる。本研究課題により、「脂溶性情報伝達物であるPS（フォスファチジルセリン）の過酸化体」を同定し、aPKCの過剰活性化を介することをはじめて明らかとした。この成果は、炎症性腸疾患や癌などの酸化ストレスを伴う病態発症および重篤化をまねく共通の分子基盤と考えられ、炎症性腸疾患や癌などの新たな治療法確立のための分子基盤として有用である。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C.2016
Author(s)
Hanaki T, Horikoshi Y, Nakaso K, Nakasone M, Kitagawa Y, Amisaki M, Arai Y, Tokuyasu N, Sakamoto T, Honjo S, Saito H, Ikeguchi M, Yamashita K, Ohno S and Matsura T
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Journal Title
Biochim Biophys Acta
Volume: 1860
Issue: 11
Pages: 2404-2415
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Enhanced Taste Sensitivity in Patients with Type 2 Diabetes Oral Preparation of High Molecular Weight Fucoidan: Fucose-containing Sulfated Polysaccharides2017
Author(s)
Chieko Sakai, Yosuke Horikoshi, Sunao Abe, Minoru Kozuki, Hisashi Shimohiro, Yoshie Ota, Hironori Sakinada, Tatsuo Takeuchi, Tsuyoshi Okura, Takeshi Kasagi, Keiichi Hanaki
Organizer
77 rd scientific sesslons American Diabetes Association（SANDIEGO. USA）
Related Report
Int'l Joint Research
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