Structural basis of potent antiperoxidation activity of the triterpene celastrol in mitochondria: effect of negative membrane surface charge on lipid peroxidation.
The structural basis of the potent inhibitory effect of the triterpene celastrol on lipid peroxidation of rat liver mitochondria initiated by adenosine 5'-diphosphate (ADP) and Fe2+ was studied in comparison with the effects of its analogs, pristimerin and acetylcelastrol. The dienone-phenol moiety and the anionic carboxyl group of celastrol were concluded to be important for their antiperoxidative action: The former moiety directly scavenges radicals and the latter donates the membrane with a negative surface charge, making it more resistant to peroxidation. Celastrol is suggested to inhibit the peroxidation of the outer and inner mitochondrial membrane by direct radical scavenging, and also to prevent the attack of oxygen radicals on the inner membrane by increasing its negative surface charge.
Sassa
H
H
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Kogure
K
K
Takaishi
Y
Y
Terada
H
H
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D004563:Electrochemistry; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers; D007425:Intracellular Membranes / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure*; D010101:Oxygen Consumption; D053978:Pentacyclic Triterpenes; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D008081:Liposomes; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D014810:Vitamin E; D000244:Adenosine Diphosphate; C050414:celastrol