The effect of superoxide generation on the ability of mitochondria to take up and retain Ca²⁺

Abstract

When heart or liver mitochondria are exposed to superoxide radicals generated from xanthine + xanthine oxidase their ability to take up and to retain Ca 2+ is impaired. The rate of oxidation of pyruvate + malate as substrates is diminished and the appearance of thiol groups when the mitochondria are supplied with these substrates is abolished. These inhibitory effects are offset if respiration is supported by succinate in presence of rotenone provided that a substrate (fl-hydroxybutyrate) is provided to maintain the reduction of NADH. The data agree with the thesis that a generation of thiol groups is essential to maintain membrane integrity and that the generation depends on provision of reduced NAD(P)H. Mitochondrial Ca 2 + Superoxide effect Thiol groups

Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury.

“…The time course of these effects varied depending on the free radical-generating system used, probably as a result of different rates of production of free radical species with the different systems. (6,(39)(40)(41)(42). In the septum, the transient increase followed by a decrease in developed tension and rise in rest tension are consistent with a progressive rise in cytosolic calcium.…”

Glycolytic inhibition and calcium overload as consequences of exogenously generated free radicals in rabbit hearts.

“…Exogenous free radicals would be expected to enhance cellular calcium loading by the known inhibition ofNa'-K+ ATPase in the surface membrane and of Ca2+-ATPase in both the sarcolemma and the sarcoplasmic reticulum (20,22,23,(62)(63)(64)(65). Free radicals are also capable ofinjuring mitochondrial Ca2+-ATPase (34). These various effects may be direct consequences of the oxidant species, or they may be mediated through end products oflipid peroxidation which could in turn react with integral membrane proteins.…”

“…These various effects may be direct consequences of the oxidant species, or they may be mediated through end products oflipid peroxidation which could in turn react with integral membrane proteins. Disruption ofcell integrity has been argued not to be necessary (17,34 (9,17,24,68). During ischemia, it has been proposed that glucose produces ATP in proximity to the sarcolemma at a critical rate to maintain calcium homeostasis, thus delaying calcium overload (24 (33).…”

Reduction of the metallochromic indicators arsenazo III and antipyrylazo III to their free radical metabolites by cytoplasmic enzymes

“…Since antipyrylazo III does not elicit such side reactions, its use should be preferred. In addition, experiments in which the effect of xanthine-xanthine oxidase on Ca2+ transport by intact mitochondria was measured by changes in arsenazo III absorbance [22] should be re-evaluated in view of the reduction of this dye by that system.…”