대한한의학회지 (The Journal of Korean Medicine)

  • 제22권3호
  • /
  • Pages.21-30
  • /
  • 2001
  • /
  • 1010-0695(pISSN)
  • /
  • 2288-3339(eISSN)
대한한의학회 (The Society of Korean Medicine)
권호 표지

$H_2O_2$에 노출된 신장 근위 세뇨관 세포에서의 세포 사망 및 DNA 손상에 대한 단삼의 효과

Effect of Salviae Radix on Cell Death and DNA Damage in Renal Proximal Tubular Cells Exposed to $H_2O_2$

  • Sung-Dae, Kim (Department of Internal Medicine, College of Oriental Medicine, Dongguk University) ;
  • Ji-Cheon, Jeong (Department of Internal Medicine, College of Oriental Medicine, Dongguk University)
  • 발행 : 2001.09.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목적 : 이전 연구에서 단삼 추출액이 강력한 항산화 작용이 있음을 확인한 바 있어 단삼 추출액이 신장세뇨관 세포에서 oxidant에 의한 세포사망 및 DNA 손상을 방지하는 지를 조사하고 이러한 효과가 지질의 과산화를 억제하는 효과에 기인하는 지를 시험하였다. 방법 : 신장 근위세뇨관 세포 유래 세포주인 opossum kidney (OK)세포를 이용하여 세포 사망은 frypan blue exclusion방법을 이용하여 평가하였고, DNA손상 정도는 double stranded DNA의 파괴를 측정하여 평가하였다. Oxidant 약물 모델로는 $H_2O_2$를 사용하였다. 결과 : $H_2O_2$는 적용시 간과 농도에 비례하여 세포 사망을 유도하였다. 단삼 추출액은 0.05% 농도에서 $H_2O_2$에 의한 세포사망 및 DNA 손상을 방지하였다. 이러한 방지효과는 $H_2O_2$ 제거 효소인 catalase와 철 착염제인 deferoxamine에 의해서도 나타났다. 그러나 강력한 항산화제인 DPPD는 $H_2O_2$에 의한 세포 사망이나 DNA손상을 방지하지 못하였다. $H_2O_2$는 세포내 ATP 농도를 감소시켰으며. 이러한 감소는 poly (ADP-ribose) polymerase억제제인 3-aminobenzamide에 의해 방지되었으나 단삼 추출액에 의해서는 영향을 받지 않았다. 3-aminobenzamide는 $H_2O_2$에 의한 세포 사망을 방지하였다. $H_2O_2$는 지질의 과산화를 증가시켰으며, 이러한 변화는 단삼 추출액과 DPPD에 의해 방지되었다 결론 : OK 세포에서 $H_2O_2$에 의한 세포사망과 DNA 손상에는 지질의 과산화가 중요한 역할을 하지 않으며, 단삼 추출액의 $H_2O_2$에 의한 세포 사망과 DNA 손상 방지 효과는 항산화 작용이 아닌 다른 기전에 기인하는 것으로 사료된다.

키워드

참고문헌

  1. J. Clin Invest. v.67 In vivo damage of rat lungs by oxygen metabolites Johnson, K.J.;Fantone, J.C.;Kaplan J.;Ward, P.A.
  2. J. Clin Invest. v.69 Intravaxcular activation of complement and acute lung injury : dependency on neutrophils and toxic oxygen metabolites Till, G.O.;Johnson, K.J.;Kunkel, R.;Ward, P.A.
  3. J. Clin Invest. v.73 Protease and oxidants in experimental pulmonary inflammatory injury Schraufstatter, U.S.;Revak, S.D.;Cochrane, C.G.
  4. J. Exp Med. v.149 Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity Nathan, C.F.;Silverstein, S.C.;Brunkner, L.H.;Cohn, Z.A.
  5. J Biol Chem v.256 Hydrogen peroxide causes the total injury to human fibroblasts exposed to oxygen radicals Simon, R.H.;Scoggin, C.H.;Patterson, D.
  6. J Clin Invest v.68 A Role of hydrogen peroxide in neutrophil-mediated destruction of cultured endothelial cells Weiss, S.J.;Young, J.;LoBuglio, A.F.;Slivka, A.
  7. J Clin Invest v.76 Alterations in ATP and energy charge in cultured endothelial and P388D1 cells following oxidant injury Spragg, R.F.;Hinshaw, D.B.;Hyslop, P.A.;Spragg, R.G.;Cochrane, C.G.
  8. Am J Physiol v.251 Reactive oxygen species : production and role in the kideny Baud, L.;Ardaillou, R.
  9. Kid Int v.29 A role of oxygen free radicals in aminonucleoside nephrosis Diamond, J.R.;Bonventre, J.V.;Karnovsky, J.
  10. Kid Int v.45 Roel fo oxidants and proteases in glomerular injury Johnson, R.J.;Lovett, D.;Lehrer, R.I.;Couser, W.G.;Klebanoff, S.J.
  11. Kid Int v.40 Reactive oxygen species and rat renal epithelial cells during hypoxia and reoxygenation Paller, M.S.;Neumann, T.V.
  12. Annu Rev Biochem v.49 Active oxygen species and the functions of phagocytic lehkocytes Badway, J.A.;Karnovsky, M.L.
  13. Biochem J v.222 Free-radical mechanisms in tissue injury Slater, T.F.
  14. J Clin Invest v.77 Oxidant injury of cells : DNA strand breaks activate polyadenosine diphosphateribose polymerase and lead to depletion of nicotinamide adenine dinucleotide Schraufstatter, I.U.;Hinshaw, D.B.;Hyslop, P.A..;Spragg, R.G.;Cochrane, C.G.
  15. Science(Wash Dc) v.215 DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate Birnboim, H.C.
  16. Biochem Biophys Acta v.654 Comparison of the effects of hydrogen peroxide and x-ray irradiation on toxicitymutation, and DNA damage/repair in mammalian cells Bradley, M.O.;Erickson, L.C.
  17. Korean Oriental Medical Society v.19 no.1 Protective effect of Salviae Radix extraction in $H_2O_2$-induced renal cell injury Kim, S.B.;Jeong, J.C.
  18. Environ Mol Mutagen v.11 DNA precipitation assay : a rapid and simple method for detecting DNA damage in mammalian cells Oliver, P.L.
  19. Anal Biochem v.86 Determination of malonadehyde precursor in tissures by thiobarbituric acid test Uchiyama, M.;Mihara, M.
  20. Anal Biochem v.72 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Bradford M.M.
  21. Pediatr Res v.25 Mechnisms of endothelial cell ATP depeltion after oxidant injury Andreoli, S.P.
  22. J Biol Chem v.263 Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide Hyslop, P.A.;Hinshaw, D.B.;Halsey, W.A.J.;Schraufstatter, I.U.;Sauerheber, R.D.;Spragg, R.G.;Jackson, J.H.;Cochrane, C.G.
  23. Arch Biochem Biophys v.286 Reactive oxygen injury to cultured puimonary artery endothelial cells: mediation by poly (ADP-ribose) polymerase activation causting NAD depletion and altered energy balance Thies, R.L.;Autor, A.P.
  24. Am J Physiol v.271 Role of reactive oxygen metabolites in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells Hagar, H.;Ueda, N.;Shah, S.V.
  25. J Clin Invest v.82 Oxidant-induced DNA damage of target cells Schraufstatter, I.;Hyslop, P.A.;Jackson, J.H.;Cochrane, C.G.
  26. Kid Int v.38 Reactive oxygen molecule-mediated injury in endothelial cells and renal tubular epithelial cells in vitro Andreoli, S.P.;Mallett, C.P.
  27. Am J Physiol v.259 Oxidative stress in isolated rat renal proximal and distal tubular cell Lash, L.H.;Tokarz, J.J.
  28. Am J Physiol v.265 Oxidant induced alteration in glucose and phosphate transport in LLC-PK2 cells : mechanisms of injury Andreoli, S.P.;McAteer, J.A.;Seifert, S.A.;Kempson, S.A.
  29. Arch Biochem Biophys v.270 Mitochondrial damage as a mechanism of cell injury in the killing of cultrued hepatocytes by tert-butyl hydroperoxide Masaki, N.;Kyle, M.E.;Serroni, A.;Farber, J.L.
  30. Toxicol Appl Pharmacol v.78 Organic hydroperoxide-induced lipid peroxidation and cell death in isolated hepatocytes Rush, G.F.;Gorski, J.R.;Ripple, M.G.;Sowinski, J.;Bugelski, P.;Hewitt, W.R.
  31. Am J Physiol v.268 Role of lipid peroxidation in $H_2O_2$-induced renal epithelial (LLC-PK1) cell injury Salahudeen, A.K.
  32. Lab Invest v.62 Biology of disease : Mechanisms of cell injury by activated oxygen species Farber, J.L.;Kyle, M.E.;Coleman, J.B.
  33. Arch Biochem Biophys v.1284 Inhibition of iodacetamide and tbutylhydroperoxide toxicity in LLC-PK1 cells by antioxidants : a role for lipid peroxidation in alkylation induced cytotoxicity Chen, Q.;Stevens, J.L.
  34. Toxicol Appl Pharmacol v.141 Differential effect of $Ca^{\2+}$ on oxidant-induced lethal cell injury and alterations of membrane transport functional integrity in renal cortical slices Kim, Y.K.;Kim, Y.H.
  35. Biochem Pharmacol v.46 Differing effects of the inhibition of poly (ADP-ribose) polymerase on the course of oxidative cell injry in hepatocytes and fibroblasts Yamamoto, K.;Tsukidate, K.;Farber, J.L.
  36. Am J Physiol v.27 Dissociation of oxidant-induced ATP depletin and DNA damage from early cytotoxicity in LLC-PK1 cells Andreoli, S.P.;Mallett, C.P.
  37. Lab Invest v.69 Cell and tissue responses to oxidative damage Jannsen, Y.M.;Houten, B.V.;Borm, P.J.A.;Mossman, B.T.
  38. Kid Int v.45 Effect of pyruvate on oxidant injury to isolated and cellular DNA Nath, K.A.;Enright, H.;Nutter, L.;Fischereder, M.;Zou, J.N.;Hebbel, R.P.
  39. J. Clin Invest. v.90 Endonuclease-induced DNA damage and cell death in oxidant injury to renal tubular epithelial cells Ueda, N.;Shah, S.V.