Effect of R-(-)-deprenyl and harmaline on dopamine- and peroxynitrite-induced membrane permeability transition in brain mitochondria.
The present study examined the effect of MAO inhibitors, deprenyl and harmaline, on the membrane permeability transition in brain mitochondria. Deprenyl, harmaline, and antioxidant enzymes (SOD and catalase) attenuated alteration of the swelling, membrane potential, cytochrome c release, and Ca2+ transport in mitochondria treated with dopamine. In contrast, deprenyl and harmaline did not reduce the peroxynitrite-induced change in membrane permeability. Deprenyl and harmaline inhibited the decrease in thioredoxin reductase activity and the thiol oxidation in mitochondria treated with dopamine but did not decrease the effect of peroxynitrite. Deprenyl and harmaline significantly decreased the formation of melanin from dopamine. The results suggest that deprenyl and harmaline may protect brain mitochondria against the toxic action of dopamine oxidation by the maintenance of thioredoxin reductase activity, inhibition of thiol oxidation, and inhibition of dopamine oxidation product formation. In contrast, MAO inhibitors may not defend brain mitochondria against damaging action of peroxynitrite.
Lee
Chung Soo
CS
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Korea. leecs@cau.ac.kr
Lee
Chung Seok
CS
Ko
Hyun Hee
HH
Song
Jin Ho
JH
Han
Eun Sook
ES
D000818:Animals; D001921:Brain / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology*; D006246:Harmaline / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010539:Permeability; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013237:Stereoisomerism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D030421:Peroxynitrous Acid; D012642:Selegiline; D006861:Hydrogen Peroxide; D006246:Harmaline; D013880:Thioredoxin-Disulfide Reductase; D004298:Dopamine