Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside.
The nitration of tyrosine caused by peroxynitrite and other reactive nitrogen species is clearly detrimental for some physiological processes; however, its signalling role is still open to controversy. Among the natural phenolics known for their ability to oppose free tyrosine nitration, isoprenylhydroquinone glucoside is investigated due to its unusual structure, which contains a simple hydroxybenzene alkylated by a hemiterpenoid moiety. This hydroquinone was shown to be an effective inhibitor of peroxynitrite-induced protein tyrosine nitration in 3T3 fibroblasts. When tested on bovine seroalbumin nitration, however, the potency was reduced by half and the effect was almost abolished in the presence of bicarbonate. In contrast, addition of this anion had no effect on the nitrite/hydrogen peroxide/hemin system. Isoprenylhydroquinone glucoside was also active in the microM range on intra- and extracellular protein-bound tyrosine nitration by phorbol 12-myristate 13-acetate-stimulated neutrophils. The effects on nitric oxide synthase expression, interleukin-1beta and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages were quite moderate. Thus, isoprenylhydroquinone glucoside is an inhibitor of protein nitration in situ, but lacks effect on the generation of either nitric oxide or inflammatory cytokines.
Olmos
Ana
A
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
Giner
Rosa-María
RM
Recio
María-Carmen
MC
Ríos
José-Luis
JL
Máñez
Salvador
S
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002474:Cell-Free System; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006418:Heme / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006873:Hydroquinones / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012235:Rhodamines; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014443:Tyrosine / Q000737:chemistry*
D005960:Glucosides; D006873:Hydroquinones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D012235:Rhodamines; D014409:Tumor Necrosis Factor-alpha; C501647:isoprenylhydroquinone glucoside; C058319:dihydrorhodamine 123; D030421:Peroxynitrous Acid; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D006418:Heme; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D013755:Tetradecanoylphorbol Acetate