| Co-Investigator(Kenkyū-buntansha) |
ギーゼラ ストルツ 米国, 国立衛生研究所 細胞生物学代謝部門, 主任研究員
スタン コルスマイヤー 米国, ワシントン大学 分子生物学, 教授
パトリック A バウエル ドイツ, ルードヴィヒ マクシミリアン大学 分子生物学, 教授
ARNE Hormgren professor Karolnska Institute, Sweden, カロリンスカ研究所 生化学, 教授
トーマス トウルツ フランス, ギュスタブー ルシー研究所 内科学, 教授
HORI Toshiyuki assistant professor, Dept. of Biological Responses Institute for Virus Research,, ウイルス研究所(生体応答学 感染防御), 助手 (70243102)
PATUICK A. Baenerle professor Ludwig-Maximilians University, FRG
THOMAS Tursg professor, Institute Gustave Roussy, France
STANLEY Korsmyer professor Washington University
GISELA Storg senior investigator National Institute for Health, USA
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| Research Abstract |
We have studied the reduction oxidation regulation mechanism (redox regulation) especially with regard to the ADF/thioredoxin under Monbusho international research program. Here we briefly report the results of this study.
A number of studies of E. Coli TRX have revealed that TRX is involved in many cellular processes as apotentendogenous thiol-related reducing agent by modulating protein-protein and protein-nucleic acid interactions through the reduction/oxidation of protein cysteine residues (Holmgren). Studies on mammalian thioredoxin system have indicated that ADF is a human homologue of thioredoxin (TRX)(Yodoi). ADF/TRX afr identical to an autocrine growth factor, 3B6-IL-1 (Tursz), produced by Epstein Barr virus (EBV) transformed B cell line, T-hybridoma-derived growth factor MP6-BSF, and eosinophil cytotoxicity enhancing factor (ECEF). Furthermore, TRX also has a radical and/or H_2O_2 scavenging activities (Yodoi). Actually, recombinant ADF/TRX protects TNFanpha or H_2O_2 induced
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cellular damage (Yodoi).
Redox regulating mechanism involving ADF/TRX has been proposed to regulate certain cellular proteins which interact with RNA or DNA (Klausner, Curran). We found that ADF/TRX enhances the binding of NF-kB to the enhancer sequence of IL-2Ralpha through the reducto/oxidation of protein cysteine residues (Yodoi, Okamoto, Arai). Recently, Ref-1 protein which has both reducing and DNA repair activities was reported and shown to be one of the target molecules of ADF/TRX (Curran). Oxidative stress may evoke intracellular signals. While Storz et al. reported inducible oxidative transcriptional mechanism, hydrogen peroxide was reported to activate NF-kappaB by Bauerle et al. We have demonstrated that oxidative stress evokes the strong tyrosine phosphorylation of lck tyrosine kinase (Yodoi).
In AIDS, the importance of thiol agents is demonstrated by Yodoi, Herzenberg, or Droge. Yodoi and oters indicated the involvement of thiol mediated regulation of cysteine/cystine transport. These analysis may reveal the abnormal thiol metabolism of HIV infected cells.
In conclusion, it is very important to continue the study of redox regulation mechanism and effect of oxidative stress on the intracellular signal transduction. Less
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