2009 Fiscal Year Final Research Report
Functional characterization of folate transport in osteoclast
| Project/Area Number |
20790141
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
INOUE Katsuhisa Nagoya City University, 大学院・薬学研究科, 准教授 (50315892)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 葉酸 / トランスポーター / 破骨細胞 / リソソーム / メトトレキサート |
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| Research Abstract |
In order to explore the possibility that the carrier-mediated folate transport system could be involved in the accumulation of methotrexate in osteoclasts, we examined the transport of folate in lysosomes isolated from the rat kidney, since lysosomal membrane has functional similarities of the ruffled border in osteoclasts. It was found that the lysosomal folate transport occurred at an acidic pH (pH 5.0 - 6.0), and was saturable with the Michaelis constant of 0.073 μM. When we examined the effect of various inhibitors for RFC1 (reduced folate carrier 1) and PCFT (proton-coupled folate transporter) on the lysosomal folate transport, the inhibition profile was found to be different from those of RFC1 and PCFT. These results suggest that lysosomes have a specific folate transport system, which has not been identified, and this transport system may be involved in methotrexate accumulation in osteoclasts.
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