| Project/Area Number |
21590185
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Kobe Pharmaceutical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TODE Chisato 神戸薬科大学, 薬学部, 講師 (20289036)
杉浦 眞喜子 神戸薬科大学, 薬学部, 准教授 (00098500)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 質量分析 / UGT1A1 / 遺伝子変異 / 酵素活性 / LC/MS / 薬物代謝 / ビリルビン / 新生児 / LC / MS |
|---|
| Research Abstract |
UDP-glucuronosyltransferase 1A1(UGT1A1) is the only physiological relevant enzyme in bilirubin glucuronidation. Mutations of the UGT1A1 gene reduce the enzyme activity, leading unconjugated hyperbilirubinemia. Bilirubin has two sites capable of glucuronidation and forms bilirubin mono-and di-glucuronides(BMG and BDG). We constructed the several expression plasmids for UGT1A1 with missense mutation(G71R, F83L, I322V, and G493R) in the gene. In this study, we established the high-throughput quantitative methods for BMG and BDG using UPLC-Orbitrap MS technique, and estimated each glucuronidation capacity of the mutated UGT1A1 by transient transfection and expression.
|
