Reactive oxygen species are involved in the stimulation of the mitochondrial permeability transition by dihydrolipoate.
Dihydrolipoic acid (DHLA) has been found to stimulate the Ca(2+)-induced mitochondrial permeability transition (MPT) in rat liver mitochondria (RLM) [Biochem. Mol. Biol. Int. 44 (1998) 127] which could be due to its prooxidant properties. We therefore investigated whether DHLA stimulated superoxide anion (O(2)(.-)) generation in RLM and in bovine heart submitochondrial particles (SMP). In RLM DHLA caused a concentration-dependent O(2)(.-) generation assayed by lucigenin chemiluminiscence. The stimulation was seen with the lowest concentrations of DHLA (5 microM) with pyruvate as the respiratory substrate, with 2-oxoglutarate or especially succinate the stimulation was less pronounced. Stimulation of O(2)(.-) production by DHLA was also observed in bovine heart SMP using an electron spin-trapping technique. Radical scavengers (butylhydroxytoluene and TEMPO) decreased O(2)(.-) generation induced by DHLA and inhibited MPT. Slight reduction of the mitochondrial membrane potential by a small amount of a protonophorous uncoupling agent also delayed the DHLA-induced MPT. These data indicate that the stimulation of MPT by DHLA is due to DHLA-derived prooxidants, i.e. stimulated production of O(2)(.-) and possibly other free radicals.
Morkunaite-Haimi
Sarune
S
Department of Applied Chemistry and Microbiology, Viikki Biocentre I, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland.
Kruglov
Alexey G
AG
Teplova
Vera V
VV
Stolze
Klaus
K
Gille
Lars
L
Nohl
Hans
H
Saris
Nils-Erik L
NE
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002417:Cattle; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; C015144:dihydrolipoic acid