1-METHYL-4-PHENYLPYRIDINUM KILLS DIFFERENTIATED PC12 CELLS WITH A CONCOMITANT CHANGE IN PROTEIN-PHOSPHORYLATION

被引:32
作者
MUTOH, T [1 ]
TOKUDA, A [1 ]
MARINI, AM [1 ]
FUJIKI, N [1 ]
机构
[1] NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892
关键词
1-METHYL-4-PHENYLPYRIDINUM; PC12; CELL; NERVE GROWTH FACTOR; S6; PROTEIN; APOPTOSIS;
D O I
10.1016/0006-8993(94)91179-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1-Methyl-4-phenylpyridinum (MPP(+)), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP(+) (100 mu M) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP(+) treatment (100 mu M) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP(+), kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP(+) neurotoxicity and/or the protection from its toxicity.
引用
收藏
页码:51 / 55
页数:5
相关论文
共 20 条
[1]   1-METHYL-4-(2'-ETHYLPHENYL)-1,2,3,6-TETRAHYDROPYRIDINE-INDUCED TOXICITY IN PC12 CELLS IS ENHANCED BY PREVENTING GLYCOLYSIS [J].
BASMA, AN ;
HEIKKILA, RE ;
SAPORITO, MS ;
PHILBERT, M ;
GELLER, HM ;
NICKLAS, WJ .
JOURNAL OF NEUROCHEMISTRY, 1992, 58 (03) :1052-1059
[2]   AURINTRICARBOXYLIC ACID RESCUES PC12 CELLS AND SYMPATHETIC NEURONS FROM CELL-DEATH CAUSED BY NERVE GROWTH-FACTOR DEPRIVATION - CORRELATION WITH SUPPRESSION OF ENDONUCLEASE ACTIVITY [J].
BATISTATOU, A ;
GREENE, LA .
JOURNAL OF CELL BIOLOGY, 1991, 115 (02) :461-471
[3]   A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE [J].
BURNS, RS ;
CHIUEH, CC ;
MARKEY, SP ;
EBERT, MH ;
JACOBOWITZ, DM ;
KOPIN, IJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (14) :4546-4550
[4]  
DISPASQUALE B, 1991, BIOCHEM BIOPH RES CO, V181, P1442
[5]   ESTABLISHMENT OF A NORADRENERGIC CLONAL LINE OF RAT ADRENAL PHEOCHROMOCYTOMA CELLS WHICH RESPOND TO NERVE GROWTH-FACTOR [J].
GREENE, LA ;
TISCHLER, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (07) :2424-2428
[6]   MPTP TOXICITY - IMPLICATIONS FOR RESEARCH IN PARKINSONS-DISEASE [J].
KOPIN, IJ ;
MARKEY, SP .
ANNUAL REVIEW OF NEUROSCIENCE, 1988, 11 :81-96
[7]   1-METHYL-4-PHENYLPYRIDINIUM ION (MPP+) - IDENTIFICATION OF A METABOLITE OF MPTP, A TOXIN SELECTIVE TO THE SUBSTANTIA NIGRA [J].
LANGSTON, JW ;
IRWIN, I ;
LANGSTON, EB ;
FORNO, LS .
NEUROSCIENCE LETTERS, 1984, 48 (01) :87-92
[8]  
Lemasters J J, 1979, Methods Enzymol, V56, P530
[9]   INHIBITORS OF PROTEIN-SYNTHESIS AND RNA-SYNTHESIS PREVENT NEURONAL DEATH CAUSED BY NERVE GROWTH-FACTOR DEPRIVATION [J].
MARTIN, DP ;
SCHMIDT, RE ;
DISTEFANO, PS ;
LOWRY, OH ;
CARTER, JG ;
JOHNSON, EM .
JOURNAL OF CELL BIOLOGY, 1988, 106 (03) :829-844
[10]   EFFECTS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND 1-METHYL-4-PHENYLPYRIDINIUM ION ON ACTIVITIES OF THE ENZYMES IN THE ELECTRON-TRANSPORT SYSTEM IN MOUSE-BRAIN [J].
MIZUNO, Y ;
SONE, N ;
SAITOH, T .
JOURNAL OF NEUROCHEMISTRY, 1987, 48 (06) :1787-1793