Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Redox regulation of cell activation and transformation by ADF/TRX (human thioredoxin) (Meeting abstract).
International Symposium on Cancer, Sapporo Cancer Seminar: Oxyradicals and Anti-oxidative Responses in Cancer. July 14-16, 1992, Sapporo, Japan, p. 46, 1992.. Unique Identifier : AIDSLINE ICDB/93690047 Taniguchi Y; Kawabe T; Masutani H; Nakamura H; Matsuda M; Okamoto T; Yodoi J; Dept. of Biological Responses, Inst. for Virus Res., Kyoto Univ.,; 53 Shogoin, Kawahara-cho, Sakyo-ku, Kyoto 606, Japan
Abstract:
Human T-lymphotropic virus type 1 (HTLV-1)-transformed T cells overexpress interleukin-2 receptor alpha chain (IL-2R alpha) and adult T-cell leukemia-derived factor (ADF), originally defined as an IL-2R inducer. Subsequent ADF cDNA cloning showed that ADF is a human homolog of thioredoxin (TRX), an endogenous thiol-reducing protein. Several cytokines, such as 3B6-IL-1, MP6-BSF and eosinophil cytotoxicity-enhancing factor, have been shown to be identical or related to ADF. In addition to cytokine/cocytokine activity to enhance the growth and activation of lymphoid cells, rADF has a potent reducing activity catalyzing the proton transfer between thiol residues of cysteine-containing proteins. rADF and thioredoxin also has a radical scavenging activity catalyzing hydrogen peroxide (H2O2). rADF also protects the cells from cytotoxicity by TNF alpha, as well as H2O2 (submitted). The expression of ADF/TRX is variable depending on the cell types and markedly enhanced in the cellular transformation following infection by HTLV-1, EBV and human papilloma virus. Because the induction of IL-2R alpha in HTLV-1 infection is dependent on NF-kappa B, we investigated whether rADF/TXR controls the regulatory effect of NF-kappa B on the IL-2R alpha-enhancer site containing NF-kappa B binding site. Binding of protein(s) to the kappa B motif in the IL-2R alpha enhancer was lost by oxidation in vitro and was completely restored by rADF/TRX in the presence of TRX reductase and NADPH. However, the activity of oxidized protein(s) binding to the kappa B motif was not restored by mutated ADF/TRX without reducing activity. When ADF/TRX was overexpressed in natural killer YT cells by transfecting its expression vector, the transcription from the promotor/enhancer of IL-2R alpha was augmented. These results demonstrated that the redox regulation via ADF/TRX may play an important role in the activation of NF-kappa B both in vitro and in vivo. As is the case of HIV LTR activation by NF-kappa B. ADF/TRX may be required for the activation of IL-2R alpha gene by NF-kappa B and possibly for the transforming process of HTLV-1-positive cells. (4 Refs)
Keywords: Cell Survival *Cell Transformation, Neoplastic *Cell Transformation, Viral Cloning, Molecular DNA Herpesvirus 4, Human/PATHOGENICITY Human HTLV-I/PATHOGENICITY Oxidation-Reduction Papillomavirus/PATHOGENICITY Thioredoxin/GENETICS/*METABOLISM ABSTRACT 930430
M9340823
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
