Mechanism accounting for the induction of nonspecific permeability of the inner mitochondrial membrane by hydroperoxides.
The effect of antioxidants on the nonspecific permeability of the inner mitochondrial membrane induced by cumene hydroperoxide or Ca(2+) has been studied. Butylated hydroxytoluene, butylated hydroxyanisole and 2,2,5,7,8-pentamethyl-6-chromanol, taken at a concentration up to 50 microM, suppress the cumene hydroperoxide-induced accumulation of lipid peroxidation products. In the same range of concentrations, these antioxidants inhibit the activation of nonspecific permeability by cumene hydroperoxide or Ca(2+). Propyl gallate, being less effective under such conditions, fails to affect the induction of nonspecific permeability. Additionally, 2,2,5,7,8-pentamethyl-6-chromanol at a concentration decreasing the accumulation of lipid peroxidation products by 70% has been shown not to increase the lag period of nonspecific permeability induction. Higher antioxidant concentrations, while leading to an increase in the lag period of nonspecific permeability induction, cause but minor suppression of lipid peroxidation. From the results obtained we can assume that free radicals formed in the course of hydroperoxide decomposition or on mitochondrial redox complex interact directly with a system responsible for nonspecific permeability or with regulating components of this system.
Novgorodov
S A
SA
A.N. Belozersky Laboratory of Molecular Biology, Moscow State University, U.S.S.R.
Gudz
T I
TI
Kushnareva
Y E
YE
Roginsky
V A
VA
Kudrjashov
Y B
YB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D004336:Drug Antagonism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats
D000975:Antioxidants; D002839:Chromans; D002084:Butylated Hydroxytoluene; D002083:Butylated Hydroxyanisole; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D006861:Hydrogen Peroxide; D010100:Oxygen; D002118:Calcium