Interactions Between Heavy Metals–Induced Cell Responses and Oxidative Stress

Abstract

Reactive oxygen species (ROS) are important regulators of physiological and pathophysiological processes and not only simply detrimental due to their chemical nature or by causing oxidative stress. In all the physiologically relevant ROS, the hydroxyl radical possesses the highest one-electron reduction potential and is reactive with almost all types of biomolecules, including lipids, proteins, and nucleic acids. As a result of their reactivity and ability to damage biological targets, hydroxyl radicals can serve as an ideal representative ROS for investigation. Thereby, recent advances in genomics and proteomics have led to the identification of a “redoxome” consisting of hundreds of proteins involved in redox systems. It comprises enzymes generating RONS such as NADPH oxidases and nitric oxide synthases, redox relays such as peroxiredoxins, thioredoxins, and glutaredoxins, enzymes degrading ROS such as superoxide dismutase or catalase, as well as numerous proteins dependent on redox modifications, which are involved in the defense against oxidant, inflammatory and/or proteotoxic stress. Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Several of metal ions in trace amounts are required for metabolism, growth, and development. Metal intoxication, particularly, neurotoxicity, genotoxicity, or carcinogenicity is widely known. Toxic xenobiotic metals (Hg, Pb, Cd, As, Sn) have no known biological function. Metal ions interact with oxygen-containing ligands through the formation of free radicals forming stable bonds with S- and N- in the form of SH or imidazole groups in proteins. Following exposure to heavy metals, their metabolism and subsequent excretion from the body depends on the presence of antioxidants (glutathione, α-tocopherol, ascorbate, etc.) associated with the quenching of free radicals by suspending the activity of enzymes (catalase, peroxidase, and superoxide dismutase).