2005 Fiscal Year Final Research Report Summary
Analysis of molecular mechanism of signal transduction pathway via cytokine receptors by bioprobes
| Project/Area Number |
15380069
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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 |
Applied biochemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
KATAOKA Takao Tokyo Institute of Technology, Center for Biological Resources and Informatics, Associate Professor, バイオ研究基盤支援総合センター, 助教授 (20242307)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Cytotoxic T lymphocyte / Epoxycyclohexenone / RKTS-33 / Caspase-8 / Acetoxycycloheximide / Apoptosis / NF-κB / TNF receptor 1 |
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| Research Abstract |
Cytotoxic T lymphocytes (CTLs) kill virus-infected cells and transformed cells via the perforin-dependent and Fas ligand-dependent pathways. Epoxycyclohexenone derivatives, ECH and RKTS-33, inhibit activation of caspase-8 and specifically block Fas-dependent apoptosis. ECH and RKTS-33 had only weak inhibitory effects on inducible expression of cell-surface Fas ligand, but strongly inhibited the Fas ligand-dependent killing pathway mediated by perforin-defective CD4^+ CTLs and concanamycin A-treated CD8^+ CTLs. However, ECH and RKTS-33 failed to prevent the perforin-dependent killing pathway mediated by CD8^+ CTLs. These results indicate that ECH and RKTS-33 are specific inhibitors for the Fas ligand-dependent killing pathway in CTL-mediated cytotoxicity.
The protein synthesis inhibitor acetoxycycloheximide (E-73) inhibits activation of the transcription factor NF-κB induced by TNF-α, but not IL-1. When human lung carcinoma A549 cells were treated with E-73, the cellular level of TNF receptor 1 decreased accompanied by the increase of cleaved TNF receptor 1 in the medium. The metalloproteinase inhibitor GM6001 and the TACE (TNF-α converting enzyme) inhibitor TAPI-2 blocked the extracellular accumulation of TNF receptor 1 induced by E-73. These results indicate that E-73 decreases cell surface TNF receptor 1 by inducing TACE-dependent shedding and thereby reduces the responsiveness of A549 cells to TNF-α.
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Research Products
(30 results)
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[Journal Article] Bioactive tetrahydrofuran lignans from Peperomia dindygulensis2005
Author(s)
Jian-lin Wu, Na Li, Toshiaki Hasegawa, Jun-ichi Sakai, Saori Kakuta, Wanxia Tang, Seiko Oka, Miwa Kiuchi, Hirotsugu Ogura, Takao Kataoka, Akihiro Tomida, Takashi Tsuruo, Masayoshi Ando
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Journal Title
J.Nat.Prod. 68(11)
Pages: 1656-1660
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Three new triterpenes from Nerium oleander and biological activity of the isolated compounds2005
Author(s)
Liwei Fu, Shujun Zhang, Na Li, Jinlan Wang, Ming Zhao, Junichi Sakai, Toshiaki Hasegawa, Tomokazu Mitsui, Takao Kataoka, Seiko Oka, Miwa Kiuchi, Katutoshi Hirose, Masayoshi Ando
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Journal Title
J.Nat.Prod. 68(2)
Pages: 198-206
Description
「研究成果報告書概要(欧文)」より
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