Ascorbate and low concentrations of FeSO4 induce Ca2+-dependent pore in rat liver mitochondria.
Oxidative stress is one of the most frequent causes of tissue and cell injury in various pathologies. The molecular mechanism of mitochondrial damage under conditions of oxidative stress induced in vitro with low concentrations of FeSO4 and ascorbate (vitamin C) was studied. FeSO4 (1-4 microM) added to rat liver mitochondria that were incubated in the presence of 2.3 mM ascorbate induced (with a certain delay) a decrease in membrane potential and high-amplitude swelling. It also significantly decreased the ability of mitochondria to accumulate exogenous Ca2+. All the effects of FeSO4 + ascorbate were essentially prevented by cyclosporin A, a specific inhibitor of the mitochondrial Ca2+-dependent pore (also known as the mitochondrial permeability transition). EGTA restored the membrane potential of mitochondria de-energized with FeSO4 + ascorbate. We hypothesize that oxidative stress induced in vitro with FeSO4 and millimolar concentrations of ascorbate damages mitochondria by inducing the cyclosporin A-sensitive Ca2+-dependent pore in the inner mitochondrial membrane.
Brailovskaya
I V
IV
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223 Russia.
Starkov
A A
AA
Mokhova
E N
EN
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D051381:Rats
D015220:Calcium Channels; D005296:Ferrous Compounds; C020748:ferrous sulfate; D004533:Egtazic Acid; D016572:Cyclosporine; D001205:Ascorbic Acid