Oxidative Stress Caused by Inactivation of Glutathione Peroxidase and Adaptive Responses

Abstract

Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. When the cellular production of ROS exceeds the cell's antioxidant capacity, cellular macromolecules such as lipids, proteins and DNA can be damaged. Because of this, 'oxidative stress' is thought to contribute to aging and pathogenesis of a variety of human diseases. However, in the last 10-15 years, a considerable body of evidence has accumulated that ROS serve as subcellular messengers, and play a role in gene regulation and signal transduction pathways, which may be involved in defensive mechanisms against oxidative stress. This review focuses on oxidative stress caused by the inactivation of glutathione peroxidase (GPx), a major peroxide scavenging enzyme. GPx is inactivated by a variety of physiological substances, including nitric oxide and carbonyl compounds in vitro and in cell culture. Decreased GPx activity has also been reported in tissues where oxidative stress occurs in several pathological animal models. The accumulation of increased levels of peroxide resulting from inactivation of GPx may act as a second messenger and regulate expression of anti-apoptotic genes and the GPx itself to protect against cell damage. These findings suggest that GPx undergoes inactivation under various conditions such as nitroxidative stress and glycoxidative stress, and that these changes are a common feature of various types of oxidative stress which may be associated with the modification of redox regulation and cellular function.

HEMA‐induced cytotoxicity: oxidative stress, genotoxicity and apoptosis

“…They found that the formation of adducts was associated with different kinetics, when the reaction occurs in human gingival fibroblasts (HGFs) or in erythrocytes, compared with methacrylates mixture with glutathione without cells, suggesting that the reaction is strongly correlated with glutathione S-transferase. Previous studies hypothesized that low concentrations of various resin (co)monomers accumulate intracellularly within a short period of time to an overall toxic level, which then results in an irreversibile exhaustion of the cells detoxifying GSH pool, thus finally causing apoptosis (Lander et al 1997, Miyamoto et al 2003. Moreover, HEMA triggers the expression of stress-responsive genes at the transcriptional level through the accumulation of ROS.…”

Effect of beef from grass or maize silage- and concentrate-fed cattle on lipid metabolism and antioxidative status of rats

“…GPx is a key enzyme involved in defence against oxidative stress by reducing hydrogen peroxide to water and also by its ability to reduce lipid hydroperoxides (Surapaneni and Venkataramana, 2007). Activation of GPx in the serum of the rats that were fed the grass-fed meat may result from the availability of glutathione or selenium in the body, but also of other redox-related molecules that cooperate with glutathione (Miyamoto et al, 2003). According to Jain et al (2000), vitamin E may restore the glutathione concentration to typical values in human erythrocytes, which may explain our results and underscore that the activity of antioxidant enzymes is related to the availability of exogenous antioxidants in the organism.…”

Reactive oxygen species delay control of lymphocytic choriomeningitis virus

“…The antioxidant glutathione is part of one of the most important redox system in mammalian cells. 44 Buthionine sulfoximine (BSO) is known to deplete glutathione, 45,46 which in turn increases ROS levels. Consistently, when mice were treated with BSO, elevated ROS production could be observed in granulocytes (Figures 6a).…”