Dossier : Antioxidants in the prevention of human diseasesSulfiredoxin: a potential therapeutic agent?
Section snippets
General introduction
Cells have evolved an intricate network of antioxidant molecules and proteins that are required to maintain homeostasis. Reactive oxygen species (ROS) are generated exogenously by environmental agents or endogenously as a consequence of normal cellular metabolic processes including, respiration. When ROS levels exceed the antioxidant capacity of cells, oxidative stress (OS) results. The toxicity of ROS is due to their ability to damage a large number of cellular constituents, of which
Srx, a novel antioxidant protein
OSR is a term that is used to describe the signaling events that occur when the intracellular OS is higher than the antioxidant capacity of the cell. Srx was first identified in Saccharomyces cerevisiae and was found to be involved in the OSR [4]. Srx is not only induced in response to treatment with H2O2 but deletion of the gene leads to a decreased resistance to H2O2. Insight into its mechanism of action was clarified when Srx was identified as a binding partner to the yeast peroxiredoxin
Glutathionylation as a post-translational modification
GSH is a critical antioxidant in the cell and its' conjugation to electrophilic compounds is essential to the detoxification pathway. We are now beginning to realize the potentially major role that GSH plays in post-translational modifications that alter cellular response to oxidative and nitrosative stress. It is not surprising that GSH is present in millimolar concentrations in the cell. In fact, the ratio of the reduced GSH pool to glutathione disulfide (GSSG) is a redox sensor and used to
Deglutathionylation as a mechanism of cellular stress regulation
Reversibility of post-translational modifications is a requisite for cellular signaling. Deglutathionylation is the removal of the GSH moiety from proteins and can occur when the environment becomes more reducing in an enzyme-dependent or -independent manner. To date, a limited number of proteins have been identified that are involved in deglutathionylation. Grx is a well-characterized protein known to be involved in both the oxidative glutathionylation and the reductive deglutathionylation
Oxidative/nitrosative stress and disease
Formation of ROS and RNS is not only the result of an exogenous insult, but a consequence of normal cellular metabolism. It is the tight regulation of these processes within the cell that allows maintenance of homeostasis and consequently a limit to the amount of damage caused by these ROS/RNS. Dysregulation leads to an accumulation of ROS/RNS resulting in cellular damage. Unfortunately however, many diseases are associated with an increase in oxidative/nitrosative damage and aging itself is
Concluding remarks
Glutathionylation is emerging as an important post-translational modification that influences a large number of proteins. The growing number of disease states that are correlated with increased glutathionylation of specific proteins highlights the need to understand the underlying mechanisms involved in the regulation of the glutathionylation and deglutathionylation pathways. The identification of Srx and its role as a novel antioxidant protein specifically involved in the deglutathionylation
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2018, Free Radical Biology and MedicineCitation Excerpt :The present study is the first to undertake a comprehensive analysis of SRXN1 function in cardiac progenitor cells. SRXN1 has been recognized as an endogenous antioxidant that protects against brain tissue damage in Parkinson's disease [37]. Recent studies have confirmed the critical role of SRXN1 in regulating oxidative stress-triggered cell death in neuronal cells [20,38] and cardiomyocytes [24].