Protective effect of harmaline and harmalol against dopamine- and 6-hydroxydopamine-induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells

D. H. Kim, Yoon Young Jang, E. S. Han, C. S. Lee

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1861-1872
Number of pages12
JournalEuropean Journal of Neuroscience
Volume13
Issue number10
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Harmine
Carbolines
Synaptosomes
Oxidopamine
PC12 Cells
Dopamine
Mitochondria
Catecholamines
Brain
Harmaline
Sulfhydryl Compounds
Antioxidants
Mitochondrial Swelling
Thioredoxin-Disulfide Reductase
Deoxyribose
Selegiline
Mitochondrial Membrane Potential
Enzymes
Membrane Potentials
Catalase

Keywords

  • β-carbolines
  • Brain mitochondria
  • Catecholamines
  • PC12 cells
  • Protection
  • Synaptosomes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Protective effect of harmaline and harmalol against dopamine- and 6-hydroxydopamine-induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells",
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.",
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author = "Kim, {D. H.} and Jang, {Yoon Young} and Han, {E. S.} and Lee, {C. S.}",
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T1 - Protective effect of harmaline and harmalol against dopamine- and 6-hydroxydopamine-induced oxidative damage of brain mitochondria and synaptosomes, and viability loss of PC12 cells

AU - Kim, D. H.

AU - Jang, Yoon Young

AU - Han, E. S.

AU - Lee, C. S.

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N2 - 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.

AB - 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.

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