Project/Area Number |
23590551
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Virology
|
Research Institution | Keio University |
Principal Investigator |
SUGIYAMA Kazuo 慶應義塾大学, 医学部, 特任准教授 (10242520)
|
Co-Investigator(Renkei-kenkyūsha) |
SAITO Hidetsugu 慶應義塾大学, 薬学部, 教授 (80186949)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | C型肝炎ウイルス / ペントースリン酸経路 / コレステロール / 脂肪酸 / Nrf2 / メタボローム / 脂肪滴 / C型肝炎ウイルス / 持続感染 / ペントースリン酸系 / 代謝 / 脂質代謝 / Hepatitis C virus / hepatocellular carcinoma / metabolome |
Research Abstract |
In this study, to explore the mechanism for metabolic alteration by hepatisis C virus (HCV), we established a hepatic cell line, HPI cell, persistently infected with HCV. This cell line accumulated massive lipid droplets showing prominent steatosis. Thus we performed integrated analysis by combining microarray and metabolomics. As a result, enhanced production of cholesterol and fatty acids by up-regulation of the rate limiting enzymes. Pentose phosphate pathway was enhanced with production of NADPH. Moreover, TCA cycle was also enhanced indicating hypermetabolic status of the HPI cell. It was speculated that constitutively activated Nrf2, which is a key transcription factor for metabolism, was attributed to the hypermetabolism of HPI cell. In conclusion, HPI cell is a useful tool for research of not only HCV but also liver metabolism.
|