Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review)

Mizushina,Yoshiyuki; Nishiumi,Shin; Nishida,Masayuki; Yoshida,Hiromi; Azuma,Takeshi; Yoshida,Masaru

doi:10.3892/ijo.2013.1771

Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity (Review)

Authors:
- Yoshiyuki Mizushina
- Shin Nishiumi
- Masayuki Nishida
- Hiromi Yoshida
- Takeshi Azuma
- Masaru Yoshida
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Affiliations: Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Kobe, Hyogo 651-2180, Japan, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
Published online on: January 15, 2013 https://doi.org/10.3892/ijo.2013.1771
Pages: 793-802

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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.

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1	Furie B and Furie BC: Molecular basis of vitamin K-dependent γ-carboxylation. Blood. 75:1753–1762. 1990.
2	Suttie JW: Synthesis of vitamin K-dependent proteins. FASEB J. 7:445–452. 1993.PubMed/NCBI
3	Shearer MJ: Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care. 3:433–438. 2000. View Article : Google Scholar : PubMed/NCBI
4	Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T and Komai M: Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem. 70:926–932. 2006. View Article : Google Scholar : PubMed/NCBI
5	Seegers WH and Bang NU: Blood Clotting Enzymology. Academic Press; New York, NY: 1967
6	Elder SJ, Haytowitz DB, Howe J, Peterson JW and Booth SL: Vitamin K contents of meat, dairy, and fast food in the U.S. diet. J Agric Food Chem. 54:463–467. 2006. View Article : Google Scholar : PubMed/NCBI
7	Tsukamoto Y, Ichise H, Kakuda H and Yamaguchi M: Intake of fermented soybean (natto) increases circulating vitamin K2 (menaquinone-7) and γ-carboxylated osteocalcin concentration in normal individuals. J Bone Miner Metab. 18:216–222. 2000.PubMed/NCBI
8	Suttie JW: The importance of menaquinone in human nutrition. Annu Rev Nutr. 15:399–417. 1995. View Article : Google Scholar : PubMed/NCBI
9	Booth SL: Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation? Nutr Rev. 68:178–181. 2010. View Article : Google Scholar : PubMed/NCBI
10	Billeter M, Bolliger W and Martius C: Untersuchungen uber die umwandlung von verfutterten K-vitamin durch austausch der seitenkette und die rolle der darmbakterien hierbei. Biochem Z. 340:290–303. 1964.(In German).
11	Davidson RT, Foley AL, Engelke JA and Suttie JW: Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr. 128:220–223. 1998.PubMed/NCBI
12	Budavari S, O’Neil MJ, Smith A and Heckelman PE: The Merck Index. Merck & Co. Inc; Rahway, NJ: 1989
13	Taggart WV and Matschiner JT: Metabolism of menadione-6,7-3H in the rat. Biochemistry. 8:1141–1146. 1969. View Article : Google Scholar : PubMed/NCBI
14	Monks TJ, Hanzlik RP, Cohen GM, Ross D and Graham DG: Quinone chemistry and toxicity. Toxicol Appl Pharmacol. 112:2–16. 1992. View Article : Google Scholar
15	O’Brien PJ: Molecular mechanisms of quinone cytotoxicity. Chem Biol Interact. 80:1–41. 1991.
16	Bolton JL, Trush MA, Penning TM, Dryhurst G and Monks TJ: Role of quinones in toxicology. Chem Res Toxicol. 13:135–160. 2000. View Article : Google Scholar : PubMed/NCBI
17	Cho AK, Schmitz DA, Ying Y, Rodriguez CE, DiStefano EW, Kumagai Y, Miguel A, Eiguren A, Kobayashi T, Avol E and Froines JR: Determination of four quinones in diesel exhaust particles, SRM 1649a, and atmospheric PM2.5. Aerosol Sci Technol. 38:68–81. 2004. View Article : Google Scholar
18	Kornberg A and Baker TA: DNA replication Chaprter. 6 2nd edition. WD Freeman and Co; New York, NY: pp. 197–225. 1992
19	Hubscher U, Maga G and Spadari S: Eukaryotic DNA polymerases. Annu Rev Biochem. 71:133–163. 2002. View Article : Google Scholar
20	Bebenek K and Kunkel TA: DNA repair and replication. Adv Protein Chem. 69:137–165. 2004.
21	Takata K, Shimizu T, Iwai S and Wood RD: Human DNA polymerase N (POLN) is a low fidelity enzyme capable of error-free bypass of 5S-thymine glycol. J Biol Chem. 281:23445–23455. 2006. View Article : Google Scholar : PubMed/NCBI
22	Loeb LA and Monnat RJ Jr: DNA polymerases and human disease. Nat Rev Genet. 9:594–604. 2008. View Article : Google Scholar : PubMed/NCBI
23	Mizushina Y, Tanaka N, Yagi H, Kurosawa T, Onoue M, Seto H, Horie T, Aoyagi N, Yamaoka M, Matsukage A, Yoshida S and Sakaguchi K: Fatty acids selectively inhibit eukaryotic DNA polymerase activities in vitro. Biochim Biophys Acta. 1308:256–262. 1996. View Article : Google Scholar : PubMed/NCBI
24	Mizushina Y, Yoshida S, Matsukage A and Sakaguchi K: The inhibitory action of fatty acids on DNA polymerase β. Biochim Biophys Acta. 1336:509–521. 1997.
25	Mizushina Y, Motoshima H, Yamaguchi Y, Takeuchi T, Hirano K, Sugawara F and Yoshida H: 3-O-methylfunicone, a selective inhibitor of mammalian Y-family DNA polymerases from an Australian sea salt fungal strain. Mar Drugs. 7:624–639. 2009. View Article : Google Scholar : PubMed/NCBI
26	Sakaguchi K, Sugawara F and Mizushina Y: Inhibitors of eukaryotic DNA polymerases. Seikagaku. 74:244–251. 2002.PubMed/NCBI
27	Mizushina Y: Specific inhibitors of mammalian DNA polymerase species. Biosci Biotechnol Biochem. 73:1239–1251. 2009. View Article : Google Scholar : PubMed/NCBI
28	Mizushina Y: Screening of novel bioactive compounds from food components and nutrients. J Jpn Soc Nutr Food Sci. 64:377–384. 2011. View Article : Google Scholar
29	Mizushina Y, Yonezawa Y and Yoshida Y: Selective inhibition of animal DNA polymerases by fat-soluble vitamins A, D, E and K, and their related compounds. Curr Enzyme Inhibition. 3:61–75. 2007. View Article : Google Scholar
30	Sasaki R, Suzuki Y, Yonezawa Y, Ota Y, Okamoto Y, Demizu Y, Huang P, Yoshida H, Sugimura K and Mizushina Y: DNA polymerase γ inhibition by vitamin K₃ induces mitochondria-mediated cytotoxicity in human cancer cells. Cancer Sci. 99:1040–1048. 2008.
31	Matsubara K, Kayashima T, Mori M, Yoshida H and Mizushina Y: Inhibitory effects of vitamin K₃ on DNA polymerase and angiogenesis. Int J Mol Med. 22:381–387. 2008.PubMed/NCBI
32	Tanaka S, Nishiumi S, Nishida M, Mizushina Y, Kobayashi K, Masuda A, Fujita T, Morita Y, Mizuno S, Kutsumi H, Azuma T and Yoshida M: Vitamin K₃ attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation. Clin Exp Immunol. 160:283–292. 2010.
33	Chinzei R, Masuda A, Nishiumi S, Nishida M, Onoyama M, Sanki T, Fujita T, Moritoh S, Itoh T, Kutsumi H, Mizuno S, Azuma T and Yoshida M: Vitamin K₃ attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway. Pancreas. 40:84–94. 2011.
34	Mizushina Y, Maeda J, Irino Y, Nishida M, Nishiumi S, Kondo Y, Nishio K, Kuramochi K, Tsubaki K, Kuriyama I, Azuma T, Yoshida H and Yoshida M: Effects of intermediates between vitamins K(2) and K(3) on mammalian DNA polymerase inhibition and anti-inflammatory activity. Int J Mol Sci. 12:1115–1132. 2011. View Article : Google Scholar : PubMed/NCBI
35	Kobayashi K, Nishiumi S, Nishida M, Hirai M, Azuma T, Yoshida H, Mizushina Y and Yoshida M: Effects of quinone derivatives, such as 1,4-naphthoquinone, on DNA polymerase inhibition and anti-inflammatory action. Med Chem. 7:37–44. 2011. View Article : Google Scholar : PubMed/NCBI
36	Aoganghua A, Nishiumi S, Kobayashi K, Nishida M, Kuramochi K, Tsubaki K, Hirai M, Tanaka S, Azuma T, Yoshida H, Mizushina Y and Yoshida M: Inhibitory effects of vitamin K₃ derivatives on DNA polymerase and inflammatory activity. Int J Mol Med. 28:937–945. 2011.
37	Huang TT and Wuerzberger-Davis SM: Sequential modification of NEMO/IKKÁ by SUMO-1 and ubiquitin mediates NF-κB activation by genotoxic stress. Cell. 115:565–576. 2003.PubMed/NCBI
38	Hayden M and Ghosh S: Signaling to NF-κB. Genes Dev. 18:2195–2224. 2004.
39	Bonizzi G and Karin M: The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25:280–288. 2004.
40	Wajant H, Pfizenmaier K and Scheurich P: Tumor necrosis factor signaling. Cell Death Differ. 10:45–65. 2003. View Article : Google Scholar : PubMed/NCBI
41	Elson CO, Sartor RB, Tennyson GS and Riddell RH: Experimental models of inflammatory bowel disease. Gastroenterology. 109:1344–1367. 1995. View Article : Google Scholar : PubMed/NCBI
42	Aggarwal BB: Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 3:745–756. 2003. View Article : Google Scholar : PubMed/NCBI
43	Rahman I, Biswas SK and Kirkham PA: Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 72:1439–1452. 2006. View Article : Google Scholar : PubMed/NCBI
44	Corda S, Laplace C, Vicaut E and Duranteau J: Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-α is mediated by ceramide. Am J Respir Cell Mol Biol. 24:762–768. 2001.PubMed/NCBI
45	Cooper HS, Murthy SN, Shah RS and Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 69:238–249. 1993.PubMed/NCBI
46	Bhattacharyya S, Dudeja PK and Tobacman JK: ROS, Hsp27, and IKKβ mediate dextran sodium sulfate (DSS) activation of IκBα, NFκB, and IL-8. Inflamm Bowel Dis. 15:673–683. 2009.
47	Mizushina Y, Hirota M, Murakami C, Ishidoh T, Kamisuki S, Shimazaki N, Takemura M, Perpelescu M, Suzuki M, Yoshida H, Sugawara F, Koiwai O and Sakaguchi K: Some anti-chronic inflammatory compounds are DNA polymerase λ-specific inhibitors. Biochem Pharmacol. 66:1935–1944. 2003.
48	Mizushina Y, Takeuchi T, Kuramochi K, Kobayashi S, Sugawara F, Sakaguchi K and Yoshida H: Study on the molecular structure and bio-activity (DNA polymerase inhibitory activity, anti-inflammatory activity and anti-oxidant activity) relationship of curcumin derivatives. Curr Bioactive Compounds. 3:171–177. 2007. View Article : Google Scholar
49	Garcia-Diaz M, Bebenek K, Sabariegos R, Dominguez O, Rodriguez J, Kirchhoff T, Garcia-Palomero E, Picher AJ, Juarez R, Ruiz JF, Kunkel TA and Blanco L: DNA polymerase λ, a novel DNA repair enzyme in human cells. J Biol Chem. 277:13184–13191. 2002.
50	Singhal RK and Wilson SH: Short gap-filling synthesis by DNA polymerase β is processive. J Biol Chem. 268:15906–15911. 1993.
51	Matsumoto Y and Kim K: Excision of deoxyribose phosphate residues by DNA polymerase β during DNA repair. Science. 269:699–702. 1995.
52	Sobol RW, Horton JK, Kuhn R, Gu H, Singhal RK, Prasad R, Rajewsky K and Wilson SH: Requirement of mammalian DNA polymerase-β in base-excision repair. Nature. 379:183–186. 1996.
53	Ramadan K, Shevelev IV, Maga G and Hubscher U: DNA polymerase λ from calf thymus preferentially replicates damaged DNA. J Biol Chem. 277:18454–18458. 2002.
54	Sugo N, Aratani Y, Nagashima Y, Kubota Y and Koyama H: Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase β. EMBO J. 19:1397–1404. 2000.PubMed/NCBI
55	Garcia-Diaz M, Bebenek K, Kunkel TA and Blanco L: Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase λ: a possible role in base excision repair. J Biol Chem. 276:34659–34663. 2001.
56	Hirose F, Hotta Y, Yamaguchi M and Matsukage A: Difference in the expression level of DNA polymerase β among mouse tissues: high expression in the pachytene spermatocyte. Exp Cell Res. 181:169–180. 1989.
57	Garcia-Diaz M, Dominguez O, Lopez-Fernandez LA, De Lera LT, Saniger ML, Ruiz JF, Parraga M, Garcia-Ortiz MJ, Kirchhoff T, Del Mazo J, Bernad A and Blanco L: DNA polymerase λ, a novel DNA repair enzyme in human cells. J Mol Biol. 301:851–867. 2000.
58	Bertocci B, De Smet A, Flatter E, Dahan A, Bories JC, Landreau C, Weill JC and Reynaud CA: Cutting edge: DNA polymerases μ and λ are dispensable for Ig gene hypermutation. J Immunol. 168:3702–3706. 2002.