| Co-Investigator(Kenkyū-buntansha) |
TAKANO Hirohisa National Institute for Environmental Studies, environmental endocrine disrupter dioxin research project, Director, 環境ホルモン・ダイオキシン研究プロジェクト, 総合研究官 (60281698)
ICHINOSE Takamichi Oita University of Nursing and Health Sciences, Professor, 教授 (50124334)
SUMI Daigo University of Taukuba, Graduate School of Comprehensive human Sciences, Lecture, 大学院・人間総合科学研究科, 講師 (30400683)
ISHII Tetsuro University of Taukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院・人間総合科学研究科, 教授 (20111370)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Research Abstract |
We found that 9,10-phenanthraquinone (9,10-PQ) is an abundant quinone in contaminated in diesel exhaust particles (DEP) and atmospheric PM2.5 and that 1,2-Naphthoquinone (1,2-NQ) is identified as an environmental quinone in DEP and atmospheric PM2.5. Such polycyclic aromatic hydrocarbon quinines are known to react readily with nucleophiles such as protein SH functions to cause alkylation of crucial cellular proteins. Alternatively, 9,10-PQ and 1,2-NQ are highly redox active molecules that can be involved in the redox cycle with their semiquinone radical anions, resulting in the formation of reactive oxygen species.
In vivo study : Forty eight hours after intratracheal injection of 9,10-PQ (1 μg/body) into mice, levels of neutrophils and eosinophils, in the bronchial alveolar lavage from 9,10-PQ exposed animals were much greater than those from control mice. Levels of macrophages were not affected at this time. Our results suggest that PQ may increase the cytokine/chemokine through presu
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mably Th2 activation, thereby causing elevated BAL levels of neutrophils and eosinophils associated with inflammation.
Ex vivo studies : 1,2-NQ caused a significant suppression of Ach-induced endothelium-dependent vasorelaxation in aortic ring, suggesting that 1,2-NQ is an environmental quinone that inhibits eNOS activity, thereby disrupting NO-dependent vascular tone. 1,2-NQ is capable of causing a concentration dependent contraction of tracheal smooth muscle in guinea pigs with EC50 value of 18.7 μM. From several lines of evidence suggested that 1,2-NQ-mediated tracheal contraction was, at least in part, attributable to protein tyrosone kinasess phosphorylation that activates capsaicin receptor, resulting in increased intracellular calcium content in the smooth muscle cells.
Cultured cells study : When we examined the effects of 9,10-PQ on A549 human pulmonary epithelial cells, 9,10-PQ induced apoptosis with a LC5O of 〜7 μM. Formation of protein carbonyls DNA fragmentation were also detected in cells after treatment with 9,10-PQ, suggesting that 9,10-PQ induces oxidative protein damage, leading to apoptosis. Less
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