| Project/Area Number |
13670529
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagasaki University |
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Principal Investigator |
EJIMA Eri (2002) Department of Medicine, Assistant professor, 医学部附属病院, 助手 (30231187)
中田 惠輔 (2001) 長崎大学, 医学部, 助教授 (40217740)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO Kazuhiko Health Research Center, Associate professor, 保健管理センター, 助教授 (00264218)
SHIRABE Susumu Department of Medicine, Associate professor, 大学院・医歯薬総合研究科, 助教授 (40264220)
江島 英理 長崎大学, 医学部・付属病院, 助手 (30231187)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | p48 / Interferon-α / eIF2 α / PKR / Hepatoma / TRAIL / IFN-α / eIF2α |
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| Research Abstract |
Double-stranded RNA-dependent protein kinase (PKR) is a key factor involved in interferon (IFN)-induced antiviral actions. Since p48, together with signal transducers and activators of transcription 1 and 2 (STAT1 and STAT2), is an indispensable mediator in IFN-α signaling pathways, we investigated the effect of p48 gene transduction on PKR expression and its activity in HuH-7 human hepatoma cells.
HuH-7 cells were infected or transfected with p48 gene expression adenoviral vector or plasmid vector, respectively, and incubated with or without IFN-α, then PKR expression and phosphorylation of α-subunit of eukaryotic protein synthesis initiation factor-2 (eIF2 α) in the cells were examined. In addition, PKR activity inhibiting protein translation was determined by the decrease of chloramphenicol acetyltransferase (CAT) gene translation or α-fetoprotein secretion.
p48 overexpression itself could not stimulate PKR expression. However, p48 overexpression in combination with interferon-α treatment caused a marked increase in PKR expression and augmented the phosphorylation of eIF2 α, by which the transfected CAT gene translation, as well as the endogenous α-fetoprotein synthesis, was blocked without affecting their mRNA levels.
These results suggest that p48 gene transduction may provide a strategy to enhance the IFN-mediated PKR expression and its activity in hepatocytes.
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