Exploration of novel factors reducing toxicity of environmental chemicals by utilizing toxicolipidomic analyses
Project/Area Number |
16H05108
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Environmental and hygienic pharmacy
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Research Institution | Showa University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
佐々木 由香 昭和大学, 薬学部, 助教 (40635108)
桑田 浩 昭和大学, 薬学部, 講師 (80286864)
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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 |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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Keywords | 環境化学物質 / 過酸化脂質 / プロスタグランジン / 脂質代謝 / 毒性軽減 |
Outline of Final Research Achievements |
In order to explore novel factors reducing toxicity of environmental chemicals, we performed toxicolipidomics, in which we comprehensively investigated chemicals-induced alterations in lipid profiles, and examined phenotypes of chemicals-exposed mice genetically modified to alter lipid metabolism. As the results, we suggested that iPLA2gamma, which has an ability to eliminate lipid peroxides, might function as a detoxifying enzyme against toxicity of several environmental chemicals. Furthermore, it was also suggested that long-chain acyl-CoA synthetase ACSL4 and some of prostaglandin terminal synthases such as mPGES-1 and PGIS might have dual functions not only as suppressors but also as accelerators of chemicals-induced toxicity.
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Academic Significance and Societal Importance of the Research Achievements |
私たちの身の回りには様々な化学物質が存在するが、その多くには毒性があり大量に摂取すれば健康被害を及ぼす。このため、化学物質とうまく付き合っていくには、その毒性発現機構や生体防御機構を明らかにすることが極めて重要である。本研究では、化学物質が毒性を発現する際の生体内標的として脂質分子に注目し研究を進め、生体防御機構の1つとして、ある種の脂質代謝酵素が生体内毒性軽減因子として機能する可能性を見出した。
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Analysis on the Substrate Specificity of Recombinant Human Acyl-CoA Synthetase ACSL4 Variants2019
Author(s)
Shimbara-Matsubayashi, S., Kuwata, H., Tanaka, N., Kato, M., Hara, S.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 5
Pages: 850-855
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-05-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] The group VIA calcium-independent phospholipase A2 and NFATc4 pathway mediates IL-1β-induced expression of chemokines CCL2 and CXCL10 in rat fibroblasts2018
Author(s)
Kuwata, H., Yuzurihara, C., Kinoshita, N., Taki, Y., Ikegami, Y., Washio, S., Hirasawa, Y., Yoda, E., Aiuchi, T., Tabe, H., Nakatani, Y., Hara, S.
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Journal Title
FEBS J.
Volume: in press
Issue: 11
Pages: 2056-2070
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of prostacyclin synthase in carcinogenesis2017
Author(s)
Sasaki, Y., Ochiai, T., Takamura, M., Kondo, Y., Yokohama, C., Hara, S.
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Journal Title
Prostaglandins Other Lipid Mediat.
Volume: 133
Pages: 49-52
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Role of group VIB calcium-independent phospholipase A2 (iPLA2γ) in carcinogenesis2016
Author(s)
Hara, S., Sasaki, Y., Morikaku, Y., Yamada, R., Hirai, R., Yoda, E.
Organizer
Lipid Mediators in Health and Disease II: From the Cutting Edge / 7th International Conference on Phospholipase A2 and Lipid Mediators: From Bench to Translational Medicine
Place of Presentation
Scripps Forum, University of California San Diego (La Jolla, USA)
Year and Date
2016-05-19
Related Report
Int'l Joint Research
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[Presentation] Role of prostacyclin synthase in chemical-induced carcinogenesis2016
Author(s)
Sasaki, Y., Endo, Y., Suzuki, Y., Kondo, Y., Yokoyama, C., Hara, S.
Organizer
2016 Japan/Korea Joint Symposium on Pharmaceutical Health Science and Environmental Toxicology
Place of Presentation
昭和大学上條講堂(東京都品川区)
Related Report
Int'l Joint Research
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[Presentation] Role of prostaglandin terminal synthases PGIS and mPGES-1 in chemical-induced carcinogenesis2016
Author(s)
Hara, S., Sasaki, Y., Endo, Y., Suzuki, Y., Yokoyama, C., Kondo, Y.
Organizer
6th European Workshop on Lipid Mediators
Place of Presentation
Goethe University in Frankfurt am Main (Frankfurt am Main, Germany)
Related Report
Int'l Joint Research
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