Neopterin activates transcription factor nuclear factor-kappa B in vascular smooth muscle cells.
We have previously shown that the pteridine compound neopterin stimulates inducible nitric oxide synthase (iNOS) gene expression in vascular smooth muscle cells in vitro. The mechanisms whereby neopterin exhibits these effects remained unclear. The present study demonstrates that neopterin induces the translocation of the transcription factor nuclear factor-kappa B (NF-kappa B) to the nucleus. Pretreatment of cells with the antioxidant pyrrolidine dithiocarbamate completely suppressed the effects of neopterin on NF-kappa B activation, iNOS gene expression, and nitric oxide release. From these data we conclude that neopterin activates the translocation of NF-kappa B subunits to the nucleus by modulating the intracellular redox state. This is one possible explanation for the impact of neopterin on iNOS gene expression.
Hoffmann
G
G
Department of Physiology, University of Bonn, Germany.
Schobersberger
W
W
Frede
S
S
Pelzer
L
L
Fandrey
J
J
Wachter
H
H
Fuchs
D
D
Grote
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta; D001483:Base Sequence; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019798:Neopterin; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D013859:Thiocarbamates / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D017931:DNA Primers; D007527:Isoenzymes; D016328:NF-kappa B; D009573:Nitrites; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D019798:Neopterin; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase