title: Inhibition of repair-related DNA polymerases by vitamin Ks, their related             quinone derivatives and associated inflammatory activity (Review).
abstract: Vitamin Ks (VKs) are fat-soluble quinone compounds known to have various             bioactivities. This review describes the inflammatory effects of VKs and their             related quinone derivatives based on DNA polymerase (pol) inhibition. VK3, but             not VK1 or VK2 (=MK-4), inhibited the activity of human pol γ, which is the DNA             replicative pol in mitochondria. Of the intermediate compounds between VK2 and             VK3 (namely MK-3, MK-2 and MK-1), MK-2 was the strongest inhibitor of mammalian             pols α, κ and λ, which belong to the B-, Y- and X-families of pols, respectively.             Among the VK3 based quinone derivatives, such as 1,4-naphthoquinone (NQ), 2-dimethyl-1,4-naphthoquinone             (1,2-dimethyl-NQ), 1,4-benzoquinone (BQ), 9,10-anthraquinone (AQ) and 5,12-naphthacenequinone             (NCQ), NQ was the strongest inhibitor of mammalian pols α and λ, in particular,             DNA repair-related pol λ. Among the all compounds tested, NQ displayed the strongest             suppression of tumor necrosis factor (TNF)-α production induced by lipopolysaccharide             (LPS) in a cell culture system using RAW264.7 mouse macrophages. NQ also suppressed             the expression of pol λ protein in these cells, after LPS-treated RAW264.7 cells             were stimulated to induce pol λ expression. In an in vivo mouse model of LPS-evoked             acute inflammation, intraperitoneal injection of NQ into mice suppressed TNF-α             production in peritoneal macrophages and serum. In an in vivo colitis mouse model             induced using dextran sulfate sodium (DSS), NQ markedly suppressed DSS-evoked             colitis. The promising anti-inflammatory candidates based on the inhibition of             DNA repair-related pols, such as pol λ, by VKs quinone derivatives, such as NQ,             are discussed.
authors: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Kobe, Hyogo 651-2180, Japan. mizushin@nutr.kobegakuin.ac.jp
authors: Yoshiyuki
authors: Y
authors: Mizushina
authors: Shin
authors: S
authors: Nishiumi
authors: Masayuki
authors: M
authors: Nishida
authors: Hiromi
authors: H
authors: Yoshida
authors: Takeshi
authors: T
authors: Azuma
authors: Masaru
authors: M
authors: Yoshida
mesh_terms: D000818:Animals; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors; D000074002:DNA Polymerase gamma; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase; D006801:Humans; D007249:Inflammation; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014812:Vitamin K / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000099270:Y-Family DNA Polymerases
chemical_list: D004256:DNA Polymerase I; D019951:DNA Polymerase beta; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D009285:Naphthoquinones; D019384:Nucleic Acid Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014812:Vitamin K; C415367:DNA polymerase beta2; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases; C035342:1,4-naphthoquinone