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 b y adenosine 5'-diphosphate (ADP) and Fe2+ was studied in comparison wi th the effects of its analogs, pristimerin and acetylcelastrol. The di enone-phenol moiety and the anionic carboxyl group of celastrol were c oncluded to be important for their antiperoxidative action: The former moiety directly scavenges radicals and the latter donates the membran e with a negative surface charge, making it more resistant to peroxida tion. Celastrol is suggested to inhibit the peroxidation of the outer and inner mitochondrial membrane by direct radical scavenging, and als o to prevent the attack of oxygen radicals on the inner membrane by in creasing its negative surface charge.