| Project/Area Number |
07407071
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
YODOI Junji Kyoto University, Inst, for Virus Research, Dept of Biological responses, Professor, ウイルス研究所, 教授 (80108993)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HORI Tohiyuki Kyoto Univ.Inst for Virus Research, Research center for Immunodeficiency virus,, ウイルス研究所, 助手 (70243102)
MAEDA Michiyuki Kyoto Univ.Inst for Chest Disease, Facility of animal experiments, Associate pro, 胸部疾患研究所, 助教授 (20027329)
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 1997: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1996: ¥6,100,000 (Direct Cost: ¥6,100,000)
|
|---|
| Keywords | Redox regulation / thioredoxin / AP-1 / transcription factor / Anti-cancer drug / Apoptosis / Ischemia / レドックス / ADF / 核タンパク質 / 細胞死 / ヒトthioredoxin / phagocyte oxidase / シクロヘキシミド / TGF-β / Yeast two hybrid / cis-element / Thioredoxin / Jun, Fos / Ref-1 / direct interaction / CDDP |
|---|
| Research Abstract |
We investigate the redfox regulation of cellular functions, poetically intra/inter cellular redox status and its regulating mechanism using molecular biological methods.
We focused the dunction of the redox catalyst, Adult T-cell leulemia derived factor (ADF)/thioredoxin (TRX) in nucleus. Firstly, we investigate the involvement of ADF/TAX in the redox regulation of early immediately gene Jun, Fos (AP-1). Redox factor-1 (Ref-1) was already identified as reducing protein for AP-1. We found the direct interaction of ADF/TRX with Ref-1 in nucleus. Its interaction has the synergistic effects for AP-1 transcription activity. ADF/TRX was enhanced DNA binding activity of mouse transcription factor PEBP2 that has Runt domain as DNA binding region. In further study, we analyze nuclear translocation of ADF/TRX and its regulatory mechanism.
In other hand, promoter region of human ADF/TRX gene was analyzed. It was observed that ADF/TRX expression was enhanced by several oxidative stress including UV irradiation and hydrogfen peroxide. The unknown 27bp sequence was identified as response element for oxidative stress. We are analyzing the element and purifying its binding protein.
In order to reveal the ADF/TRX function, we conducted ADF/TRX gene disruption to analyze knock-out mice. Gene disruption was succeeded, but heterozygous gene defected mice was not borne. Genetic and anatomical analysis indicate ADF/TRX gene disruption causes early embryonic lethality.
Finally, we investigate the cellular protective effect of ADF/TRX against anticancer drags including cis-Diamminedichloroplatinum (II) (CDDP). ADF/TRX expression and ADF/TRX promoter activity were up-regulated and by CDDP treatment. ADF/TRX over-expression transformant cells resist the cytotoxicity of CDDP.In also treatment of bleomycine that is another snti-cancer drug, ADF/TRX has the protective effect against cytotoxity of bleomycine.
|
