Dual activity of pyrrolidine dithiocarbamate on kappa B-dependent gene expression in U937 cells: I. Regulation by the phorbol ester TPA.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Dual activity of pyrrolidine dithiocarbamate on kappa B-dependent gene expression in U937 cells: I. Regulation by the phorbol ester TPA.

Cell Signal. 1999 Jul;11(7):479-89. Unique Identifier : AIDSLINE MED/99334230
Watanabe K; Kazakova I; Furniss M; Miller SC; Signal Transduction Laboratory, SRI International, Menlo Park, CA; 94025, USA.

Abstract: Pyrrolidine dithiocarbamate (PDTC) has been widely used as an inhibitor of the nuclear factor-kappa B, (NF-kappa B) signalling pathway. Here, we show that kappa B-dependent reporter gene expression induced by low concentrations of 12-O-tetradecanoylphorbol-13-acetate (TPA) is potentiated by PDTC in the human pro-monocytic U937 cell line. The stimulatory effect of PDTC on kappa B-dependent gene expression was shown with a 4 x kappa B chloramphenicol acetyltransferase construct and required an intact kappa B element in the human immunodeficiency virus long terminal repeat (HIV-1 LTR). Unexpectedly, an HIV-1 LTR construct with a mutation of the activator protein 2 (AP-2) binding site located between the two kappa B elements was unresponsive to the stimulatory effect of PDTC with TPA. The stimulation or inhibition of kappa B-dependent gene expression was dependent on PDTC pre-treatment and the concentration of TPA. No stimulatory effect on HIV-1 LTR activity was observed with the metal chelator dipyridyl or the anti-oxidant N-acetyl-L-cysteine. These results are consistent with the hypothesis that PDTC treatment potentiated kappa B-dependent gene expression in a manner dependent on the concentration of TPA.

Keywords: JOURNAL ARTICLE Chelating Agents Chloramphenicol O-Acetyltransferase/GENETICS Gene Expression Regulation *Gene Expression Regulation, Viral Genes, Reporter Human *HIV Long Terminal Repeat HIV-1/*GENETICS Metals NF-kappa B/GENETICS/*METABOLISM Pyrrolidines/*METABOLISM/PHARMACOLOGY Support, U.S. Gov't, P.H.S. Tetradecanoylphorbol Acetate/*METABOLISM/PHARMACOLOGY Thiocarbamates/*METABOLISM/PHARMACOLOGY Time Factors Transcription Factor AP-1/METABOLISM U937 Cells
991230
A99C1083

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