title: Protective effect of boldine on dopamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells.
abstract: Boldine ([S]-2,9-dihydroxy-1,10-dimethoxyaporphine) has been shown to exert antioxidant and anti-inflammatory effects. The present study elucidated the protective effect of boldine on catecholamine-induced membrane permeability transition in brain mitochondria and viability loss in PC12 cells. Dopamine (200 microM) and 6-hydroxydopamine (6-OHDA, 100 microM) attenuated Ca(2+) and succinate-induced mitochondrial swelling and membrane potential formation. Boldine (10-100 microM) and 10 microg/mL of superoxide dismutase (SOD) or catalase reduced the effect of catecholamine oxidation on brain mitochondria. Boldine, SOD, and catalase decreased catecholamine-induced mitochondrial cytochrome c release. Antioxidant enzymes attenuated the depressant effect of catecholamines on mitochondrial electron flow, whereas boldine did not reduce it. Boldine inhibited the catecholamine-induced decrease in thioredoxin reductase activity and the increase in thiol oxidation in mitochondria. It also showed a scavenging action on hydrogen peroxide and hydroxyl radicals and decreased the formation of melanin from dopamine. Boldine and antioxidant enzymes decreased the dopamine-induced cell death, including apoptosis, in PC12 cells. The results suggest that boldine may attenuate the catecholamine oxidation-induced brain mitochondrial dysfunction and decrease the dopamine-induced death of PC12 cells through a scavenging action on reactive oxygen species and inhibition of melanin formation and thiol oxidation.
authors.affiliation: Department of Neurology, College of Medicine, Chung-Ang University, Seoul, South Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Youn
authors.forename: Oh Sang
authors.initials: OS
authors.lastname: Kwon
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Song
authors.forename: Yong Kyu
authors.initials: YK
authors.lastname: Shin
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004347:Drug Interactions; D004579:Electron Transport / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D001060:Aporphines; D002395:Catecholamines; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D008543:Melanins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; C011686:boldine; D013880:Thioredoxin-Disulfide Reductase; D004298:Dopamine