PMID- 10405758 OWN - NLM STAT- MEDLINE DCOM- 19990927 LR - 20190921 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 11 IP - 7 DP - 1999 Jul TI - Dual activity of pyrrolidine dithiocarbamate on kappa B-dependent gene expression in U937 cells: I. Regulation by the phorbol ester TPA. PG - 479-89 AB - 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. FAU - Watanabe, K AU - Watanabe K AD - Signal Transduction Laboratory, SRI International, Menlo Park, CA 94025, USA. FAU - Kazakova, I AU - Kazakova I FAU - Furniss, M AU - Furniss M FAU - Miller, S C AU - Miller SC LA - eng GR - GM48229/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Chelating Agents) RN - 0 (Metals) RN - 0 (NF-kappa B) RN - 0 (Pyrrolidines) RN - 0 (Thiocarbamates) RN - 0 (Transcription Factor AP-1) RN - 25769-03-3 (pyrrolidine dithiocarbamic acid) RN - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Chelating Agents MH - Chloramphenicol O-Acetyltransferase/genetics MH - Gene Expression Regulation MH - *Gene Expression Regulation, Viral MH - Genes, Reporter MH - *HIV Long Terminal Repeat MH - HIV-1/*genetics MH - Humans MH - Metals MH - NF-kappa B/genetics/*metabolism MH - Pyrrolidines/*metabolism/pharmacology MH - Tetradecanoylphorbol Acetate/*metabolism/pharmacology MH - Thiocarbamates/*metabolism/pharmacology MH - Time Factors MH - Transcription Factor AP-1/metabolism MH - U937 Cells EDAT- 1999/07/16 00:00 MHDA- 1999/07/16 00:01 CRDT- 1999/07/16 00:00 PHST- 1999/07/16 00:00 [pubmed] PHST- 1999/07/16 00:01 [medline] PHST- 1999/07/16 00:00 [entrez] AID - S0898-6568(99)00023-6 [pii] AID - 10.1016/s0898-6568(99)00023-6 [doi] PST - ppublish SO - Cell Signal. 1999 Jul;11(7):479-89. doi: 10.1016/s0898-6568(99)00023-6.