Pyrrolidine dithiocarbamate prevents IL-1-induced nitric oxide synthase mRNA, but not superoxide dismutase mRNA, in insulin producing cells.
We presently investigated the effects of pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor kappa B (NF-kappa B), on the induction of nitric oxide synthase (iNOS) and manganese superoxide dismutase (MnSOD) mRNAs by IL-1 beta in insulin-producing RIN cells. PDTC decreased by 90% both IL-1 beta-induced increase in medium nitrite accumulation (an indicator of NO production) and induction of iNOS mRNA expression. However, PDTC did not prevent induction of MnSOD mRNA by IL-1 beta. PDTC induced an early (45 min) expression of c-fos mRNA and potentiated IL-1 beta-induced c-fos expression. Our data suggest that NF-kappa B activation is necessary for iNOS, but not for MnSOD, mRNA expression in insulin producing cells.
Bedoya
F J
FJ
Department of Medical Cell Biology, Uppsala University, Sweden.
Flodström
M
M
Eizirik
D L
DL
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D007340:Insulinoma; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D019001:Nitric Oxide Synthase; D010190:Pancreatic Neoplasms; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D013859:Thiocarbamates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D007328:Insulin; D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D011759:Pyrrolidines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000594:Amino Acid Oxidoreductases