1-methyl-4-phenyl-pyridinium ion (MPP+) causes DNA fragmentation and increases the Bcl-2 expression in human neuroblastoma, SH-SY5Y cells, through different mechanisms.
Apoptosis has been shown to be induced by some pathological stimuli. MPP+ is a neurotoxin and an inducer of parkinsonism. When SH-SY5Y cells, human neuroblastoma cell line, were treated with MPP+, cell death estimated by lactate dehydrogenase (LDH) leakage assay occurred. The cell death was associated with the DNA fragmentation into nucleosomal fragments at 180 bp, suggesting that MPP(+)-induced cell death of SH-SY5Y cells occurs through apoptosis. Although SH-SY5Y cells natively express Bcl-2 protein, which inhibits apoptosis, the level of Bcl-2 protein in SH-SY5Y cells increased with increases in the treatment periods of MPP+. MPP+ inhibits the mitochondrial respiratory chain. The other inhibitors of the mitochondrial respiratory chain, antimycin A and oligomycin, also caused cell death associated with DNA fragmentation, but did not increase the Bcl-2 protein level, suggesting that an MPP(+)-induced apoptosis may be due to the inhibition of the mitochondrial respiratory chain but the MPP(+)-induced increase in the Bcl-2 protein level is not due to it. A protein kinase inhibitor, staurosporine, inhibited the MPP(+)-induced increase in the Bcl-2 protein level, but not the MPP(+)-induced cell death. These results also suggest that the mechanism by which MPP+ increases the Bcl-2 protein level is different from that of MPP(+)-induced cell death.
Itano
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Y
Department of Pharmacology, Hokkaido University, Sapporo, Japan.
Nomura
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Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000968:Antimycin A / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019254:Genes, bcl-2 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009447:Neuroblastoma; D009840:Oligomycins / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009840:Oligomycins; D000968:Antimycin A; D007770:L-Lactate Dehydrogenase; D019311:Staurosporine; D015655:1-Methyl-4-phenylpyridinium