Pyrrolidine dithiocarbamate (PDTC) increases TNF-α mRNA stability

A. Nathens, R. Bitar, J. Marshall, R. Watson, A. Dackiw, O. Rotstein

Research output: Contribution to journalArticlepeer-review

Abstract

The intracellular redox state has important modulatory effects on cell activation. We set out to determine the effect of PDTC, a cell permeant antioxidant, on endotoxin (LPS) induced macrophage (M"t>) TNF-a secretion. M4> derived from the murine monocyte-macrophage cell line 3-114 were incubated with LPS (10 |lg/ml) ±PDTC (1 mM) or pyroglutamic acid (PGA.l mM) for 4 hours. TNF was quantitated by ELISA and mRNA expression by Northern analysis. TNF mRNA was normalized to 18s rRNA. Mφ Mφ+PDTC Mφ+LPS Mφ+LPS Mφ+LPS +PDTC +PGA TNF(ng/ml) 0.27±0.08 1.27±0.8 17.1±4.2 54.9±9.518.3+41 TNF mRNA 0.01±0.01 Q.01±0.01 0.38±0.2 0.79±0.3Data are mean±SEM of 3-6 separate studies.p<.05 vs MO +LPS (ANOVA) PDTC significantly potentiated LPS induced M3> TNF secretion and TNF mRNA accumulation. PGA, a cyclic molecule similar in structure to PDTC, but without antioxidant properties, had no effect. To determine the mechanism for this effect, the rate of mRNA degradation in LPS treated cells was determined following transcriptional arrest using actinomycin D. PDTC significantly increased TNF mRNA half life in LPS treated M(35.6±1.4 vs 70±11.2 min, p<.05). Thus, these data demonstrate that antioxidants may modulate cell activation through stabilization of labile mRNA transcripts.

Original languageEnglish (US)
Pages (from-to)A1050
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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