Effect of Thyroid State on Characteristics Determining the Susceptibility to Oxidative Stress of Mitochondrial Fractions from Rat Liver

Abstract

We have studied biochemical and functional characteristics of three mitochondrial fractions resolved by differential centrifugation from the liver of rats in different thyroid states. In particular, the relation between cytochrome and antioxidant content of the mitochondria and their oxygen consumption and response to oxidative stress has been investigated. The cytochrome content is greater in the fractions at higher density, whereas the opposite pattern is shown for antioxidant level. These biochemical characteristics seem to determine functional ones. In fact, the fraction at higher density exhibit greater oxygen consumption and smaller capacity for opposing a oxidative stress. A similar dependence of functional characteristics on biochemical ones was found in altered thyroid states. Hypothyroidism is associated with decreased cytochrome content and oxygen consumption and increased antioxidant level and effectiveness in responding to oxidative stress. The treatment of thyroidectomized rats with triiodothyronine leads to reversion of such a pattern. We are inclined to explain the differences in susceptibility to oxidative stress of the mitochondria by a modulation exerted by thyroid hormone, during the normal maturation process, on their cytochrome content. In effect, such a content is able to determine both respiratory characteristics and sensitivity to pro-oxidants of mitochondria. This sensitivity and the decrease of antioxidants, possibly due to free radical production associated with the increased oxygen flux, make the mitochondria less able to respond to an oxidative challenge.

Mitochondria in Exercise-Induced Oxidative Stress

“…This view has been supported by recent studies showing that the mitochondrial population of the liver could be resolved by differential centrifugation (at 1,000, 3,000 and 10,000 g, respectively) in fractions representing different forms in the mitochondrial growing-maturation-degradation cycle [112]. Such fractions are characterized by different oxidative and antioxidant capacities and effectiveness to oppose oxidative stress [112]. In particular, the light fractions (M 3 and M 10 fractions), with high oxidative capacity and low susceptibility to oxidative stress, represent transitional forms in the process of development into the heavy mitochondrial structures (M 1 fraction) exhibiting low oxidative capacity and high susceptibility to oxidative stress.…”

“…The focal nature of the mitochondrial derangement was explained by McCutcheon et al [98] admitting that the mitochondrial population of muscle consists of mitochondria of different ages and thus of varying susceptibility to exercise-induced alterations. This view has been supported by recent studies showing that the mitochondrial population of the liver could be resolved by differential centrifugation (at 1,000, 3,000 and 10,000 g, respectively) in fractions representing different forms in the mitochondrial growing-maturation-degradation cycle [112]. Such fractions are characterized by different oxidative and antioxidant capacities and effectiveness to oppose oxidative stress [112].…”

“…This view has been supported by the finding that long-lasting exercise modifies the composition of mitochondrial population by reducing the amount of proteins recovered in the M 1 fraction and increasing the oxidative capacity and the amount of proteins recovered in the M 10 fraction [33]. If extended to muscle, the above results suggest that long-lasting exercise can exert harmful effects on the mitochondria population because it reduces the amount of the mature mitochondria characterized by high oxidative capacity and high efficiency in synthesizing ATP [112,113], and increases the amount of degenerating or disrupted mitochondria with low functionality. On the other hand, under conditions inducing ROS production, including exercise, the rate of mitochondrial biosynthesis appears to increase in various tissues [115][116][117][118].…”

“…The ability of mitochondrial fractions to withstand oxidative challenge may have important implications for the protein turnover and the dynamics of the mitochondrial population under conditions leading to increased ROS production. Changes found in liver mitochondrial fractions from hyperthyroid rats suggested that the amount of damaged mitochondria in the M 10 fraction increased during oxidative stress [112,114]. This view has been supported by the finding that long-lasting exercise modifies the composition of mitochondrial population by reducing the amount of proteins recovered in the M 1 fraction and increasing the oxidative capacity and the amount of proteins recovered in the M 10 fraction [33].…”

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…It has been demonstrated that hyperthyroidism leads to accelerated free radical formation [183]. Conversely, increased free radical formation enhances intracellular scavenging enzymes, like SOD, in experimentally induced hyperthyroidism [141].…”