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Increased DNA Damage Induced by Glycation Propagator

Glycation propagator에 의한 DNA damage 증가

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

Abstract

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.

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.

Keywords

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