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, Y. Y. Jang, E. S. Han, C. S. Lee

Research output: Contribution to journalArticlepeer-review

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 - Jun 26 2001
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this