| 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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| Budget Amount *help |
¥215,670,000 (Direct Cost: ¥165,900,000、Indirect Cost: ¥49,770,000)
Fiscal Year 2017: ¥30,420,000 (Direct Cost: ¥23,400,000、Indirect Cost: ¥7,020,000)
Fiscal Year 2016: ¥38,610,000 (Direct Cost: ¥29,700,000、Indirect Cost: ¥8,910,000)
Fiscal Year 2015: ¥35,750,000 (Direct Cost: ¥27,500,000、Indirect Cost: ¥8,250,000)
Fiscal Year 2014: ¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2013: ¥63,440,000 (Direct Cost: ¥48,800,000、Indirect Cost: ¥14,640,000)
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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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