Effect of disulfiram (DS) on mitochondria from rat hippocampus: metabolic compartmentation of DS neurotoxicity.
This experiment was designed to study the acute effects of disulfiram on mitochondrial enzymes in nonsynaptic and synaptic mitochondria from rat hippocampus. Cytochrome c oxidase, monoamine oxidase-B, glycerolphosphate acyltransferase and beta-hydroxybutyrate dehydrogenase were studied. Differences in enzyme activity were seen in controls. Cytochrome c oxidase activity was higher in synaptic mitochondria whereas glycerolphosphate acyltransferase activity was higher in nonsynaptic mitochondria. Mitochondria from disulfiram treated rats, particularly synaptic mitochondria, exhibited lower specific activities of cytochrome c oxidase and monoamine oxidase-B. These alterations were not limited to either the inner or outer mitochondrial membrane. Transmission electron microscopy revealed that mitochondria from disulfiram treated rats were severely altered in isolated preparations as well as in those from whole tissue. This study shows that disulfiram exerts a differential effect on mitochondrial subpopulations.
Simonian
J
J
College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439.
Haldar
D
D
Delmaestro
E
E
Trombetta
L D
LD
D000818:Animals; D004221:Disulfiram / Q000633:toxicity*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D006884:Hydroxybutyrate Dehydrogenase / Q000378:metabolism; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006884:Hydroxybutyrate Dehydrogenase; D008995:Monoamine Oxidase; D003576:Electron Transport Complex IV; D005992:Glycerol-3-Phosphate O-Acyltransferase; D004221:Disulfiram