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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

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.

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


Information in this article was accurate in December 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.