Role of ABC protein in hepatic protection and application to hepatic surgery.
| Project/Area Number |
16390371
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Akita University |
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Principal Investigator |
YAMAMOTO Yuzo Akita University, Gastroenterological surgery, Professor, 医学部, 教授 (70281730)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Satoshi Akita University, Gastroenterological surgery, Lecturer, 医学部, 講師 (40333934)
KUME Makoto Akita University, Gastroenterological surgery, Assistant professor, 医学部, 助手 (00372326)
YOSHIOKA Masato Akita University, Gastroenterological surgery, Clinical fellow, 医学部, 医員 (40375275)
稲垣 暢也 秋田大学, 医学部, 教授 (30241954)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | ABC protein / ATP sensitive potassium channel / Ischemia-reperfusion injury of the liver / Preconditioning / ABCタンパク質 / K_<ATP> channel / liver / RT-PCR / preconditioning / Kir / SUR |
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| Research Abstract |
In this research project, we investigated the role of ATP-binding cassette protein (ABC protein) for hepatic protection to reduce the ischemia-reperfusion injury of the liver. Especially we focused on the function of ATP-sensitive potassium channel (K-ATP channel), which contributes for cell protection by controlled ionic flow. The cell protective mechanism by K-ATP channel of the myocardium is noted universally. However, its contribution in the liver is not clear. Therefore, expression and function of K-ATP channel in the liver was studied.
First, we examined the existence of K-ATP channel in the liver. K-ATP is composed of Kir6.x (6.1 or 6.2) and SUR (SUR1 or SUR2) subunits. From mRNA expression using RT-PCR and Northern blotting methods, we found the existence of Kir6.1/SUR2B complex as a K-ATP channel subunit in the liver. Furthermore, we separated the composed cells of the liver to parenchymal cells (PCs) and non-parenchymal cells (NPCs). Kir6.1/SUR2B complex exsisted in NPCs. In c
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ontrast, mRNAs of Kir6.1, 6.2, SUR1, 2A and 2B were detected in PCs. Protein expression of Kir was detected in PCs using Western blot analysis, while SUR expression was not detected. Then we confirmed the existence of K-ATP channel from changes of mRNA expression by preconditioning using channel opener or blocker before ischemia-reperfusion. Channel blocker decreased mRNA expression of SUR1. Accordingly, the existence of cells having SUR1 was proved in the liver.
Since endothelial cells are expected to be the location of K-ATP channel in the liver, we applied gene transfection eliminating the cytokine related transcriptional factors, because endothelial cells product various cytokine related factors under the ischemia-reperfusion injury. These factors modify the results of cytoprotection by K-ATP channel. We developed and proved that naked oligonucleotide was transfected to endothelial cells. To clear the role of K-ATP channel in endothelial cells using this new gene transfection method is necessary from now. Less
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Report
(3 results)
Research Products
(29 results)
