Premium
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
Author(s) -
Kim Dong Hyun,
Jang Yoon Young,
Han Eun Sook,
Lee Chung Soo
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01563.x
Subject(s) - harmaline , chemistry , dopamine , hydroxydopamine , monoamine oxidase , mitochondrion , superoxide dismutase , pharmacology , synaptosome , oxidative stress , viability assay , biochemistry , reactive oxygen species , harmine , endocrinology , biology , enzyme , dopaminergic , in vitro
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 µ m dopamine or 100 µ m 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 Ca 2+ uptake induced by 10 µ m 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.