Identification of primary molecule leading to aminoglycoside-induced nephrotoxicity and optimization of molecular-targeted approach for preventing aminoglycoside toxicity
| Project/Area Number |
23590182
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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 |
Medical pharmacy
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| Research Institution | Hiroshima University |
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Principal Investigator |
NAGAI Junya 広島大学, 大学院医歯薬保健学研究院, 准教授 (20301301)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | アミノグリコシド系抗生物質 / 腎毒性 / 腎移行 / エンドサイトーシス / チャネル / 腎尿細管上皮細胞 / カチオンチャネル / ゲンタマイシン / 腎近位尿細管上皮細胞 / HK-2細胞 / メガリン |
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| Research Abstract |
In this study, we investigated the molecular mechanisms underlying entry of an aminoglycoside antibiotic gentamicin in renal proximal tubular cell lines OK and HK-2. In OK cells expressing a multi-ligand endocytic receptor megalin, gentamicin was taken up into the cells via endocytosis-dependent pathway. On the other hand, in HK-2 cells with little megalin expression, endocytosis-independent pathway, but not endocytosis-dependent pathway, was shown to be involved in gentamicin uptake. In addition, it was suggested that the endocytosis-independent uptake of gentamicin in HK-2 cells is, at least in part, due to transport via TRPV cation channel. When gentamicin is transported via a channel-dependent pathway into renal tubular cells, gentamicin directly enters the cytoplasm, where gentamicin potently affects mitochondrial function leading to cell death. Taken together, it is likely that activation of TRPV cation channel activity increases the risk of aminoglycoside-induced nephrotoxicity.
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Characterization of Protamine Uptake by Opossum Kidney Epithelial Cells2013
Author(s)
Nagai, J., Komeda, T., Katagiri, Y., Yumoto, R., Takano, M.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 36
Issue: 12
Pages: 1942-1949
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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