TY - JOUR
T1 - 1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation
AU - Mutoh, Tatsuro
AU - Tokuda, Akira
AU - Marini, Ann M.
AU - Fujiki, Norio
N1 - Funding Information:
We thank Drs. G Guroff (NICHD, NIH, Bethesda, MD), M. Naoi (Nagoya Institute of Technology, Nagoya, Japan) and T. Nagatsu (Fujita Gakuen Health University, Toyoake, Japan) for their generous gifts of NGF and MPP +, respectively. We also thank Dr. J.P. Schwartz (NINDS, NIH, Bethesda, MD) for her stimulating discussion at the beginning of this work. This work is partly supported by a Grant-in-Aid Scientific Research on General Sciences and on Priority Areas of the Ministry of Education, Science and Culture, Japan to T.M.
PY - 1994/10/24
Y1 - 1994/10/24
N2 - 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 μM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 μM) 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.
AB - 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 μM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 μM) 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.
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U2 - 10.1016/0006-8993(94)91179-7
DO - 10.1016/0006-8993(94)91179-7
M3 - Article
C2 - 7834384
AN - SCOPUS:0027993385
VL - 661
SP - 51
EP - 55
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -