Abstract
The present study elucidated the protective effect of β-carbolines (harmaline, harmalol and harmine) against oxidative damage of brain mitochondria, synaptosomes and PC12 cells induced by either dopamine or 6-hydroxydopamine. Harmaline, harmalol and antioxidant enzymes (superoxide dismutase/SOD and catalase) decreased the alteration of mitochondrial swelling and membrane potential induced by 200 μM dopamine or 100 μM 6-hydroxydopamine. Deprenyl attenuated the dopamine-induced mitochondrial dysfunction but did not reduce the effect of 6-hydroxydopamine. While β-carbolines inhibited the electron flow in' mitochondria, they did not enhance the depressant effect of catecholamines. β-carbolines and antioxidant enzymes reversed the depression of synaptosomal Ca2+ uptake induced by 10 μM catecholamines. The compounds inhibited the catecholamine-induced thioredoxin reductase inhibition, thiol oxidation and carbonyl formation in mitochondria and synaptosomes. β-carbolines decreased the reactive species-induced deoxyribose degradation. Harmaline and harmalol reduced the catecholamine-induced loss of the transmembrane potential and of cell viability in PC12 cells. β-carbolines alone did not show a significant cytotoxic effect on PC12 cells. The results suggest that β-carbolines may attenuate the dopamine- or 6-hydroxydopamine-induced alteration of brain mitochondrial and synaptosomal functions, and viability loss in PC12 cells, by a scavenging action on reactive oxygen species and inhibition of thiol oxidation.
Original language | English (US) |
---|---|
Pages (from-to) | 1861-1872 |
Number of pages | 12 |
Journal | European Journal of Neuroscience |
Volume | 13 |
Issue number | 10 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Brain mitochondria
- Catecholamines
- PC12 cells
- Protection
- Synaptosomes
- β-carbolines
ASJC Scopus subject areas
- General Neuroscience