Effects of sesquiterpene lactones on mitochondrial oxidative phosphorylation.
1. The toxic plant sesquiterpene lactones, helenalin, hymenoxon, mexicanin-E, tenulin, dihydrogriesenin, and psilotropin which were isolated from Helenium, Hymenoxys, and Geigeria spp markedly inhibited "state 3" respiration in mouse hepatic mitochondria. With the exception of dihydrogriesenin and psilotropin, all the other sesquiterpene lactones stimulated "state 4" respiration. 2. The sesquiterpene lactones also stimulated ATPase activity in the presence of Mg2+ ions and caused mitochondrial swelling in buffer solutions containing magnesium, sodium, ammonium and potassium chloride salts. 3. The number of alkylating sites present in a sesquiterpene lactone appears to be related to the inhibitory activity on mitochondrial oxidative phosphorylation, however, the structure-activity relationship of these lactones is not clear at present. 4. Mitochondria prepared from the liver of ethoxyquin hydrochloride-fed mice were less susceptible to sesquiterpene lactone-mediated inhibition of mitochondrial oxidative phosphorylation.
Narasimham
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Department of Veterinary Physiology and Pharmacology Texas A & M University, College Station 77843.
Kim
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HL
Safe
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D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D007783:Lactones; D009840:Oligomycins; D012717:Sesquiterpenes; D013438:Sulfhydryl Compounds; D000251:Adenosine Triphosphatases