1-O-hexyl-2,3,5-trimethylhydroquinone inhibits IkappaB phosphorylation and degradation-linked inducible nitric oxide synthase expression: beyond antioxidant function.
Inducible nitric oxide (NO) production in macrophages plays an important role in atherosclerosis, the protective effects of vitamin E and its derivatives perhaps being partly mediated by alteration in this parameter. We have investigated the influence of a novel synthesized vitamin E derivative, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), on NO production in the RAW 264.7 mouse macrophage cell line. HTHQ dose-dependently inhibited lipopolysaccharide (LPS)-induced NO production through reducing LPS-triggered inducible nitric oxide synthase (iNOS) expression. The phosphorylation and subsequent degradation of IkappaB caused by LPS in RAW 264.7 cells was markedly blocked. The free radical scavenging activity of HTHQ was only 2-fold that of vitamin E, whereas its inhibition of NO production was found to be nearly 500-fold stronger. Our results indicated that HTHQ suppressed NO production in macrophages by blocking IkappaB degradation and thus inhibiting iNOS expression. The inhibitory activity of HTHQ on NO production did not parallel its free radical scavenging activity, implying a possible involvement of additional functions.
Liu
Wei
W
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Japan.
Itoigawa
Masataka
M
Miki
Tokutaro
T
Nishikawa
Hiroshi
H
Sugiyama
Satoru
S
Ishikawa
Naohisa
N
D000818:Animals; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000037:antagonists & inhibitors; D006873:Hydroquinones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects
D016166:Free Radical Scavengers; D006873:Hydroquinones; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C081906:1-O-hexyl-2,3,5-trimethylhydroquinone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse