RESUMEN
The mechanism of uncoupling by lauryl sulfate (LS) has been studied. The very fact that uncoupling by low concentration of LS (a strong acid) resembles very much that by fatty acids (weak acids) was used as an argument against the fatty acid cycling scheme of uncoupling where protonated fatty acids operate as a protonophore. We have found that rat liver and heart muscle mitochondria can be uncoupled by low (70 microM) LS concentration in a fashion completely arrested by the ATP/ADP antiporter inhibitor carboxyatractylate (CAtr). On the other hand, uncoupling by two-fold higher LS concentration is not sensitive to CAtr. Addition of oleate desensitizes mitochondria to low LS so that addition of bovine serum albumin becomes necessary to recouple mitochondria. The data are accounted for assuming that low LS releases endogenous fatty acids from some mitochondrial depots, and these fatty acids are responsible for uncoupling. As to high LS, it causes a nonspecific (CAtr-insensitive) damage to the mitochondrial membrane.
Asunto(s)
Ácidos Grasos/química , Mitocondrias Hepáticas/química , Membranas Mitocondriales/química , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Desacopladores/química , Adenosina Difosfato/química , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Animales , Antiportadores/antagonistas & inhibidores , Antiportadores/química , Antiportadores/metabolismo , Atractilósido/análogos & derivados , Atractilósido/química , Atractilósido/farmacología , Ácidos Grasos/metabolismo , Mitocondrias Hepáticas/metabolismo , Membranas Mitocondriales/metabolismo , Ratas , Dodecil Sulfato de Sodio/farmacología , Tensoactivos/farmacología , Desacopladores/farmacologíaRESUMEN
The hypothesis that a non-coupled alternative oxidase of plant mitochondria operates as an antioxygen defence mechanism [Purvis, A.C. and Shewfelt, R.L., Physiol. Plant. 88 (1993) 712-718; Skulachev, V.P., Biochemistry (Moscow) 59 (1994) 1433-1434] has been confirmed in experiments on isolated soybean and pea cotyledon mitochondria. It is shown that inhibitors of the alternative oxidase, salicyl hydroxamate and propyl gallate strongly stimulate H2O2 production by these mitochondria oxidizing succinate. Effective concentrations of the inhibitors proved to be the same as those decreasing the cyanide-resistant respiration. The inhibitors proved to be ineffective in stimulating H2O2 formation in rat liver mitochondria lacking the alternative oxidase.
Asunto(s)
Peróxido de Hidrógeno/metabolismo , Mitocondrias/enzimología , Oxidorreductasas/antagonistas & inhibidores , Animales , Antioxidantes , Respiración de la Célula/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/enzimología , Proteínas Mitocondriales , Pisum sativum/enzimología , Proteínas de Plantas , Cianuro de Potasio/farmacología , Galato de Propilo/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Salicilamidas/farmacología , Glycine max/enzimología , Ácido Succínico/metabolismoRESUMEN
The effect of thyroxine on Ca2+-dependent mitochondrial permeability transition has been examined. It is shown that 40 microM thyroxine induces high amplitude swelling and decrease in membrane potential in Ca2+-loaded rat liver mitochondria, both in the presence and absence of cyclosporin A. Thyroxine-induced decrease in membrane potential is partially or completely reversed by addition of EGTA into the incubation medium. Nigericin and ADP are shown to prevent, or significantly delay, the effects of thyroxine on both mitochondrial swelling and membrane potential, whereas nicotinamide potentiates the permeabilisation of mitochondria. It is suggested that thyroxine induced reversible, cyclosporin A-insensitive permeability transition pore (PTP) opening in the inner mitochondrial membrane.
Asunto(s)
Calcio/farmacología , Ciclosporina/farmacología , Membranas Intracelulares/ultraestructura , Mitocondrias Hepáticas/ultraestructura , Tiroxina/farmacología , Adenosina Difosfato/farmacología , Animales , Ácido Egtácico/farmacología , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/fisiología , Ionóforos/farmacología , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Dilatación Mitocondrial/efectos de los fármacos , Niacinamida/farmacología , Nigericina/farmacología , Permeabilidad/efectos de los fármacos , Ratas , Desacopladores/farmacologíaAsunto(s)
Adenosina Trifosfato/metabolismo , Carbonil Cianuro p-Trifluorometoxifenil Hidrazona/farmacología , Ionóforos/farmacología , Cetocolesteroles/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Nitrilos/farmacología , Desacopladores/farmacología , Animales , Hidrólisis , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/fisiología , Protones , RatasRESUMEN
Studies have been made of the role of NADPH and NADH in carboxylation of alpha-ketoglutarate to isocytrate in the cytoplasm and mitochondria of the brain and liver in ontogenesis of hens. In both fractions of the liver, the reaction in the presence of NADPH is more intensive than that in the presence of NADH, being more intense in the cytoplasm than in mitochondria; during embryogenesis, the rate of the reaction increases up to hatching, decreasing at later stages of ontogenesis. No significant changes in the rate of carboxylation were observed during ontogenesis in the presence of NADH. In the brain, the reaction rate in the presence of NADH is higher than that in the liver, being lower in the presence of NADPH. In contrast to that in the liver, NADPH-dependent reaction in the brain is more intensive in mitochondrial fraction. The rate of both reactions, after the initial increase in embryogenesis, decreases at early postnatal stages, except NAD-dependent reaction which is sharply increased in brain cytoplasm of adult hens.