Abstract
Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term “oxidative stress” is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.
Highlights
Oxygen is a predominant element on earth and occurs mainly in compound with other elements as oxides
Generation of H2 O2 is mainly triggered by plasma membrane NADPH oxidases (NOX) and by the dissipation of superoxide anion by superoxide dismutases (SODs)
Further complexity is introduced by inter-radical reactions and thiol exchange reactions, that result in the generation of higher order polysulfides (H2 S(n), RS(n) H, RS(n) R; R = Cys, GSH, H)
Summary
Oxygen is a predominant element on earth and occurs mainly in compound with other elements as oxides. Dioxygen from a physical perspective is relatively inert but is transformed in enzymatic reactions by living organisms to become part of the biomass Byproducts of such reactions are oxygen radicals which are highly reactive and readily oxidize proteins and lipids and are termed “reactive oxygen species” (ROS) [1]. Reactive species are messengers, which are regulated and have a high specificity of action This condition—called “para-hormesis” by Forman and coworkers—ideally allows signaling without tissue damage [2]. This process certainly is not perfect, living organism undergo ageing, which goes hand in hand with the accumulation of oxidatively modified biomolecules.
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