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Glycation propagator에 의한 DNA damage 증가

Increased DNA Damage Induced by Glycation Propagator

  • 손태건 (부산대학교 약학과) ;
  • 곽이섭 (동의대학교 레저스포츠학과) ;
  • 진영완 (동의대학교 레저스포츠학과)
  • 발행 : 2004.06.01

초록

Glycation 반응은 glucose와 amino group 간에 일어나는 비효소적 축합 반응인 maillard 반응의 초기 반응으로 non enzymatic glycation 이라고도 한다. 생체내 glycation 반응을 통해 다수의 dicarbonyl화합물이 생성되고, 이들 dicarbonyl들 중에서 매우 반응성이 큰 것으로 확인된 glyoxal과 methylglyoxal과 catalase를 반응 시켜 glycation catalase의 활성 변화를 확인하였다. Non-glycated catalase에 비해 glycation catalase에서 구조적 인 modification과 degradation이 일어났으며, glycation반응 시간에 따라 활성이 크게 저하되는 것으로 확인 할 수 있었다. 특히 glycation 반응 시간 20일 경과 이후 glycation catalase 경우 활성이 거의 상실한 것으로 나타났다 Glyoxal과 methylglyoxal의 농도를 달리 해서 DNA와 반응 시켜 glycation propagator에 의한 직접적인 DNA damage를 확인 한 결과 Glyoxal과 methylglyoxal의 농도와 반응 시간에 따라 DNA mobility sit의 차이를 나타냈다. Fenton reaction 조건에 glyoxal과 methylglyoxal에 의해 활성이 저하된 catalase를 첨가 시켜 8-OH-dG의 생성을 확인한 결과 두 glycation propagator와의 반응 시간 의존적으로 8-OH-dG의 생성이 증가함을 보였다. 이상의 결과를 통해 glyoxal과 methylglyoxal의 antioxidant의 glycation은 oxidative stress의 증사를 유발해 생체내 활성 산소로부터 방어 기작에 심각한 문제를 야기하는 것으로 사료된다.

Glyoxal or methylglyoxal was incubated with catalase in 0.24 M sodium phosphate buffer (pH 7.4) at 37$^{\circ}C$. Dicarbonyls modify and inactivate catalase. Plasmid DNA that is directly incubated with glycation propagators, glyoxal and methylglyoxal, showed different DNA mobility shift compared to nomal plasmid DNA. When plasmid DNA is added in Fenton reaction with glycated catalase, plasmid DNA was significantly strand broken and 8-hydroxydeoxyguanosine production was time dependently increased. These results suggest that glycation of antioxidant is synergistic effect to oxidative stress.

키워드

참고문헌

  1. Biophysical Chemistry v.105 Unusal susceptibility of heme proteins to damage by glucose during non-enzymatic glycation Brain,L.C.;A.A.Booth;P.Todd;B.G.Hudson;R.G.Khalifah https://doi.org/10.1016/S0301-4622(03)00100-5
  2. Annu. Rev. Med v.46 Advanced Protein Glycosylation in diabetes and aging Brownlee,M. https://doi.org/10.1146/annurev.med.46.1.223
  3. J. Am. Geria. Soc. v.33 Hypothesis glucose as a mediator of aging Cerami,A.
  4. Hoppe-Seyler's Z. Physiol. Chem. Bd v.363 Inactivation of bovine kidney B-N-Acetyl-D-glucosaminidase by nonenzymatic glycosylation Dolhofer,R.;A.Siess;O.H.Wieland https://doi.org/10.1515/bchm2.1982.363.2.1427
  5. Ph. D. thesis, Dept. of Food Eng Biotechnology. Yonsei University Studies on Glycation Propagator under physiological condition Eum,S.Y.
  6. Agric. Biol. chem v.50 Role of sugar fragmentation in early stage browning of amino acid Hayashi,T.;M.Namiki https://doi.org/10.1271/bbb1961.50.1965
  7. J. Biochem v.382 glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase Hong,Y.A.;J.H.John
  8. Nephrol. Dial. Transplant. v.11 no.supp15 Oxidative stress caused by glycation of Cu, Zn-superoxide dismutase and its effects on intracellular components Junichi,F.;M.Theingi;O.Ayako;K.Hideaki;T.Naoyuki
  9. International Journal of biological macromolecules v.33 Oxidative damage of DNA by the reaction of amino acid with methylglyoxal in the presence of Fe(III) Kang,J.H. https://doi.org/10.1016/S0141-8130(03)00064-3
  10. Toxicology. Letters v.145 Oxidative damage of DNA induced by methylglyoxal in vitro Kang,J.H. https://doi.org/10.1016/S0378-4274(03)00305-9
  11. Nucleic acids research v.12 no.4 Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents Kasai,H.;S.Nishimura
  12. J. Biol. Chem v.262 no.35 Glycation and Inactivation of Human Cu-Zn-Superoxide Dismutase Katsura,A.;M.Shiro;F.Shigeru;I.Hidenobu;I.Kiyoshi;T.Naoyuki
  13. J. Gerontol v.44 An emerging hypothesis: Synergistic induction of aging by free radicals and Maillard reaction Kistal,B.S.;B.P.Yu
  14. biochemical and Biophysical Research communication v.192 no.2 Strand breaks in DNA induced by a Thiol/Fe(III)/O₂mixed Function oxidase system and its protection by a yeast antioxidant protein Kwon,S.J.;K.Kim;H.Kim;I.K.Yoon;J.W.Park https://doi.org/10.1006/bbrc.1993.1481
  15. U.S. Dept. Agr. Report v.68 no.47 Loew.O.
  16. Diabetes v.41 no.Suppl.2 Lipoprotein glycation and its metabolic on sequences Lyons,T.J. https://doi.org/10.2337/diab.41.2.S67
  17. J. Biochem. Molecular. Toxicology v.17 no.1 Diabetes, Oxidative stress, and antioxidants: A Review Maritim,A.C.;R.A.Sanders;J.B.Watkins https://doi.org/10.1002/jbt.10058
  18. Method of enzymology v.186 Measurement of 8-hydroxy-2'-deox-yguanosine in DNA and urine by high-performance liquid chromatograph with electrochemical detection Mark,K.S.;J.W.Park;C.C.Kenneth;J.G.Carlos;N.A.Bruce https://doi.org/10.1016/0076-6879(90)86146-M
  19. J. Biol. Chem v.254 Functional properties of the glycosylated minor components of human adult hemoglobin McDonald,M.J.;R.Shapiro;M.Blechman;H.F.Bunn;R.W.Noble
  20. Mutat. Res. v.251 Iron is the intracellular metal involved in the production of DNA damage by oxygen radicals Mello-Flho,A.C.;R.Meneghini https://doi.org/10.1016/0027-5107(91)90220-I
  21. Free radical Biology and Medicine v.23 no.5 Iron homeostasis, oxidative stress, and DNA damage Meneghini,R. https://doi.org/10.1016/S0891-5849(97)00016-6
  22. The maillard reaction in aging, Diabetes and Nutrition Toward maillard reaction in aging Monnier,V.M.;Baynes,J.W.;Monnier,V.M.;Alan,R.
  23. J. Biol Chem v.271 Protein cross-linking by Maillard reaction-Isolation, Characterization, and in vivo detection of a Iysine-Iysine Cross-link derived from methylglyoxal Nagaraj,R.H.;I.N.Shipanova;F.M.Faust https://doi.org/10.1074/jbc.271.32.19338
  24. Dialysis-Related Amyloidosis Contrib Nephrol v.112 Glycation of Metal-Containing Proteins such as Cu, Zn-superoxide Dismutase, Ceruloplasmin, and Ferritin: Possible Implication for DNA Damage in vivo Naoyuki,T.;K.Hideaki;N.I.Kazi;H.Sakuo;M.Theingi
  25. J. Biol. Chem v.267 Sitespecfic and random fragmentation of Cu, Zu-superoxide dismutase by glycation reaction Ookawara,T.;N.Kawamura;Y.Kitagawa;N.Taniguchi
  26. Carcinogenesis v.10 no.5 Detection of DNA adducts by high-performance liquid chromatography with electrochemical detection Park,J.W.;C.C.Kenneth;Ames,B.N. https://doi.org/10.1093/carcin/10.5.827
  27. BBA Glutathione/${Fe}^{3+}$/O₂-mediated DBA Strand breaks and 8-hydroxydeoxyguanosine formation Park,J.W.;A.F.Robert.
  28. Archives of Biochemistry and Biophysics v.403 Inactivation of cellular enzymes by carbonyls and proteinbound glycation/glycoxidation products Philip,E.M.;R.T.Dean;M.J.Davies https://doi.org/10.1016/S0003-9861(02)00222-9
  29. Proc. Natl. Acad. Sci v.85 Normal oxidative damage to mitochondrial DNA is extensive Richard,C.;J.W.Park;B.N.Ames https://doi.org/10.1073/pnas.85.17.6465
  30. Biochem. Biophys. Acta v.964 Nonenzymatic glycation of antithrombin III in vitro Sakurai,T.;J.P.Biossel;F.Bunn https://doi.org/10.1016/0304-4165(88)90034-7
  31. J. Biol. Chem v.259 Nonenzymatic glycosylation of human serum albumin alters its conformation and function Shaklai,N.;R.Garlick;H.F.Bunn
  32. Kor. Biochem J. v.23 Formation of dicarbonyl compound from protein reducing sugar reaction system Shin,D.B.;R.Yang;W.C.Shin;S.H.Oh
  33. Free. Radic. Biol. Med. v.16 Powerful transition-metal ion chelator that inhibit copperbut potentiates iron-driven, fenton-type reactions Standstorm,B.E.;M.Granstorm;S.L.Marklud https://doi.org/10.1016/0891-5849(94)90141-4
  34. Ann. Chim. Phys v.11 Thenard.L.J.
  35. Biosci. Biotech. Biochem v.56 Glycation of myofibrillar protein in aged rat and mice Watanabe,H.;M.Ogasawara;N.Suzuki;Nishizawa;K.Ambo https://doi.org/10.1271/bbb.56.1109
  36. Experientia v.40 The autoxidation of glyceraldehyde and other simple monosaccharides Wolff,S.P.;M.J.C.Crabbe;P.J.Thornalley https://doi.org/10.1007/BF01947562