| Project/Area Number |
16K00563
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
LEE Jin-Yong 愛知学院大学, 薬学部, 准教授 (80581280)
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| Co-Investigator(Kenkyū-buntansha) |
徳本 真紀 愛知学院大学, 薬学部, 講師 (90614339)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | カドミウム / 腎毒性 / BIRC3 / アポトーシス / ネクロプトーシス / 腎障害 / カスパーゼ３ / 腎特異性 / ARNT / 人体有害物質 |
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| Outline of Final Research Achievements |
Cadmium is one of the harmful heavy metals, which induce severe renal toxicity. This study was conducted to clarify the role of BIRC3 in the renal toxicity of cadmium. First, it is demonstrated that cadmium suppresses BIRC3 gene expression and reduces intracellular protein levels in HK-2 human renal proximal tubular epithelial cells. Knockdown of BIRC3 activated caspase 3 in HK-2 cells as well as cadmium. Furthermore, activation of caspase 3 by BIRC 3 gene expression reduction is a cadmium-specific action in renal proximal tubular cells. On the other hand, BIRC3 knockdown as well as cadmium treatment significantly induced extracellular release of HMGB-1, which is an index of necroptosis, in HK-2 cells. Moreover, phosphorylation of RIPK1 by cadmium was also observed. From the above results, it is suggested that suppression of BIRC3 expression by cadmium not only causes apoptosis but also induction of necroptosis in renal proximal tubular cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、カドミウムの毒性発現および防御機構におけるBIRC3の役割を明らかにすることを目的とした。本研究は、本申請者がカドミウム毒性発現に関わる新たな細胞内因子として見いだしたBIRC3の役割解明しており、学術的独自性がある。しかも、カドミウムの毒性発現におけるBIRC3の役割解析は世界で初めての報告となり、学術的独自性の高いといえる。本研究によって、新たなカドミウム毒性発現機構が明らかになり、カドミウム毒性研究、さらに金属毒性学研究の発展にも大きく貢献することである。
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