Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease.

Abstract

The mode of cell death in Parkinson's disease (PD) substantia nigra is uncertain. However, evidence is accumulating that certain of the biochemical abnormalities present in PD nigra at the time of death may precipitate apoptosis. We have investigated the mode of death induced by complex I inhibition of dopaminergic cell cultures, and our results suggest that both 1-methyl-4-phenylpyridinium and rotenone cause apoptosis at low concentrations and necrosis at high concentrations. This dose-dependent shift in the mode of cell death induced by these mitochondrial toxins may have important implications for the mechanisms of neuronal cell death in PD.

• Authors: A Hartley, J M Stone, C Heron, J M Cooper, A H Schapira
• Journal: Journal of neurochemistry (J Neurochem) Vol. 63 Issue 5 Pg. 1987-90 (Nov 1994) ISSN: 0022-3042 [Print] England
• PMID: 7931358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Rotenone
• NADH, NADPH Oxidoreductases
• Electron Transport Complex I
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (pharmacology)
• Animals
• Apoptosis (drug effects)
• Dose-Response Relationship, Drug
• Electron Transport Complex I
• NADH, NADPH Oxidoreductases (antagonists & inhibitors)
• Necrosis (pathology)
• PC12 Cells
• Parkinson Disease (pathology)
• Rats
• Rotenone (pharmacology)
• Substantia Nigra (pathology)