Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons.
Apoptosis is a prominent mechanism of programmed cell death in lymphocytes and in cancer cells not previously found in neurons. We have identified apoptosis and internucleosomal DNA degradation in cultures of cerebellar granule neurons. 1-methyl-4-phenylpyridinium, a selective neurotoxin that destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome, increases the rate of apoptosis and kills cerebellar granule cells in culture via induction of programmed cell death. Inhibition of gene expression in granule cells with cycloheximide prevents the MPP(+)-induced apoptosis and the DNA fragmentation. Our findings demonstrate a new pathway of neuron death and suggest the possibility that neurodegenerative diseases may result from the inappropriate activation of programmed cell death by apoptosis.
Dipasquale
B
B
Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-0010.
Marini
A M
AM
Youle
R J
RJ
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000302:isolation & purification; D007700:Kinetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D004247:DNA; D003513:Cycloheximide; D015655:1-Methyl-4-phenylpyridinium