2017 Fiscal Year Final Research Report
Comprehensive study on environmental electrophiles-mediated signal transduction pathways regulated by reactive sulfur species
| Project/Area Number |
25220103
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Risk sciences of radiation and chemicals
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
赤池 孝章 東北大学, 医学系研究科, 教授 (20231798)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
石井 功 昭和薬科大学, 薬学部, 教授 (90292953)
西田 基宏 大学共同利用機関法人自然科学研究機構(岡崎共通研究施設), 岡崎統合バイオサイエンスセンター, 教授 (90342641)
新開 泰弘 筑波大学, 医学医療系, 助教 (10454240)
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| Project Period (FY) |
2013-05-31 – 2018-03-31
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| Keywords | 親電子物質 / シグナル伝達 / 環境応答 / 化学修飾 / 活性イオウ分子 |
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| Outline of Final Research Achievements |
Environmental electrophiles covalently bind to thiol groups in proteins to form protein adducts. In the present study, we found that exposure of cultured cells to environmental electrophiles such as naphthoquinones, methylmercury, cadmium and crotonaldehyde at lower concentrations activated redox signaling pathways through covalent modification of sensor proteins. However, exposure to these electrophiles at higher concentrations disrupted the redox signaling pathways and caused substantial cytotoxicity through non-selective covalent modification of cellular proteins. It was also found that while reaction of environmental electrophiles with reactive sulfur species (RSS) resulted in formation of their sulfur adducts, knockdown of cystathionine γ-lase, an enzyme to produce RSS, enhanced the modulation of redox signaling and toxicity in vitro and in vivo, whereas treatment with Na2S4 diminished these phenomena during exposure to environmental electrophiles.
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| Free Research Field |
環境医学
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