1996 Fiscal Year Final Research Report Summary
Molecular Mechanism for Redox-Regulation of the JE gene
| Project/Area Number |
07672382
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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 |
Biological pharmacy
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| Research Institution | Showa University |
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Principal Investigator |
NOSE Kiyoshi Professor, Showa University School of Pharmaceutical Sciences, 薬学部, 教授 (70012747)
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| Co-Investigator(Kenkyū-buntansha) |
MASHIMO Jun'ichi Assistant professor, Showa University School of Pharmaceutical Sciences, 薬学部, 助手 (60054045)
EGAWA Kiyoshi Lecture, Showa University School of Pharmaceutical Science, 薬学部, 講師 (00095879)
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| Project Period (FY) |
1995 – 1996
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| Keywords | active oxygen / JE gene / NFkappaB / transcription |
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| Research Abstract |
The JE gene encodes a secreted protein that participates in inflammation and immunological responses. Its expression is induced by various growth factors and stimuli. We previously showed that the induction of JE by phorbol ester was inhibited by scavengers of oxygens, and active oxygens seemed to be involved in the signal transduction of JE gene expression. In the present study, we focused to identify transcriptional regulatory region of the JE gen, especially active oxygen-responsive element in 5'-upstream region. Using CAT as a reporter, various deletions of 5'-upstream region of rat JE gene were constructed, and transcriptional response was measured by transfection into Balb 3T3 cells. About 400 bp element that locates between-1600 to-1200 bp upstream was found to participate in transcriptional activation through active oxygens, and this element contained well known NFkappaB sites. Gel shift assay using the NFkappaB as a probe, activation of binding activity of Balb 3T3 unclear extract by phorobol ester was inhibited in the presence of radical scavengers. The above results indicates that active oxygens produced from cells stimulated with phorbol ester have positive effect on the activation of NFkappaB that is most important in the transcriptional activation of JE gene.
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[Publications] Patel, K., Connoly, D.J., Amthor, H., Nose, K., and Cooke, J: "Cloning and early dorsal axial expression of Flik, a chiken follistatin-related gene : Evidence for involvement in dorsalization. neural induction" Developmental Biology. 178. 327-342 (1996)
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[Publications] Shibanuma.M., Mochizuki, E., Maniwa, R., Mashimo, J., Nishiya, N., Imai, J., Takano, T., Oshimura, M., and Nose, K: "Induction of senescencelike phonotypes by the forced expression of hic-5 encoding a novel LIM motif protein in immortalized human fibroblasts" Mol.Cell.Biol. (in press). (1997)
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