흰쥐 태아 중뇌 배양세포에서 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine의 독성: 2',7',-Dichlorofluorescin diacetate를 이용한 연구

  • 김율아 (한림대학교 의과대학 약리학교실) ;
  • 조용준 (한림대학교 의과대학 약리학교실) ;
  • 김용식 (서울대학교 의학대학 약리학교실) ;
  • 김영희 (한림대학교 의과대학 약리학교실)
  • Published : 1993.12.01

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known dopamine neuron-specific toxin. But the involvement of oxidative damage in the pathogenesis of MPTP-induced parkinsonism is still uncertain. In this study, by using 2',7',-dichlorofluorescin diacetate(DCFH-DA) that detects intracellular oxidative processes, the effect of MPTP on dichlorofluorescein fluorescence in dissociated cells from fetal rat mesencephalon in culture was investigated. At 7th day in culture, cells were loaded with DCFH-DA, and exposed to 1 mM MPTP or MPP+. MPTP induced dichlorofluorescein-fluorescence which was peaked at 3 min and mostly faded away 30 min after MPTP treatment.

Keywords

References

  1. J. Immunol. v.130 Flow cytometric studies of oxidative product formation by neutrophils:a graded response to membrance stimulation Bass,D.A.;Parce,J.W.;Dechatelet,L.R.;Szejda,P.;Seeds.M.C.;Thomas,M.
  2. Proc. Natl. Acad. Sci. USA. v.80 A primate model of parkinsonism:selective destruction of dopaminergic neurons in the pars compacta of the substansia nigra by 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine Burns,R.S.;Chiueh,C.C.;Markey,S.P.;Ebert,M.H.;Jacobwitz,D.M.;Kopin,I.J.
  3. Life. Sci. v.36 Potential bioactivaton pathways for the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) Castagnoli,N.;Chiba,K.;Trevor,A.J.
  4. Biochem. Res. Commun. v.120 Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase Chiba,K.;Trevor,A.;Castagnoli,N.
  5. Eur. J. Pharmacol. v.119 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) neurotoxicity in mice is enhanced by pretreatment with diethyldithiochromate Corsini,GU.;Pintus,S.;Chiueh,C.C.;Weiss,J.F.;Kopin,I.J.
  6. Biochem. Biophys. Res. Commun. v.137 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)causes rapid ATP depletion in isolated hepatocytes di Monte,D.;Jewell,S.A.;Ekstrom,G.;Saandy,M.S.;Smith,T.P.
  7. Chem-Biol. Interactions v.62 Role of 1-methyl-4-phenylpyridinium ion formation and accumulation in 1-mehtyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity to isolated hepatocytes di Monte,D.;Ekstrom,G.;Shinka,T.;Smith,M.T.;Trevor,A.J.;Castagnoli,N.
  8. Eur. J. Pharmacol. v.97 Neurotoxicity of meperidine analogue MPTP in brain catecholamine neuron in the mouse Hallman,H.;Olson,L.;Jonsson,G.
  9. Neuropharmacol. v.23 Effect of MPTP on nigrostriatal dopamine in mice Heikkila,R.E.;Cabbot,R.A.;Manzino,L.;Duvoisin,R.C.
  10. Naure. v.311 Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidase inhibitors Heikkila,R.E.;Manzino,L.;Cabbat,F.S.;Duvoisin,R.C.
  11. Life. Sci. v.38 1-Methyl-4-phenylpyridine(MPP+) induces oxidative stress in the rodent Johannessen,J.N.;Adams,J.D.;Schuller,H.M.;Bacon,J.P.;Markey,S.P.
  12. Ann. Rev. Neurosci. v.11 MPTP toxicity:implications for research in Parkinson's disease Kopin,I.J.;Markey,S.P.
  13. Brain. Res. v.292 Selective nigral toxicity after systemic administration of 1-methyl-1,2,3,6-tetrahydropyridine(MPTP)in the squirrel monkey Langston,W.J.;Forno,L.S.;Rebert,C.S.;Irwin,I.
  14. Science v.225 Pargyline prevents MPTP-induced parkinsonism in primates Langston,W.J.;Irwin,I.;Langston,E.B.;Forno,L.S.
  15. Toxicol. Appl. Phamacol. v.104 Organometal-induced increases in oxygen reactive species: the potential fo 2'7'-dichlorofluorescin diacetate as ad index of neurotoxic damage Lebel,C.P.;Ali,S.F.;McKee,M.;Bondy,S.C.
  16. Science v.224 Trail of ironies to parkinson's disease Lewin,R.
  17. Life Sci. v.36 Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine Niklas,W.J.;Vyas,I.;Heikkila,R.E.
  18. Biochem. Biophys. Res. Commun. v.134 Uptake of the neurotoxin 1-methyl-4-phenylpyridine(${MPP}^+$)by mitochondria and its relation to the inhibiton of the mitochondrial oxidation of (${NAD}^+$)-linked substrares by (${MPP}^+$) Ramsey,R.R.;Salach,J.I.;Singer,T.P.
  19. Biochem. Pahrmacol. v.37 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) and free radical in vitro Rosset,Z.L.;Sotgiu,A.;Sharp.D.E.;Hajiconstantinou,M.;Neff,N.H.
  20. Biochem. Pharmacol. v.31 Activation on pharmacologic agent to radical intermediates. Implications for the role of free radicals in drug action and toxicity Trush,M.A.;Mimnaugh,E.G.;Gram,T.E.
  21. J. Neurochem. v.46 Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine:inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenyl-pyridinium Vyas,I.;Heikilla,R.E.;Nicklas,W.J.