Oxidative stress and redox regulation: adaptation, damage, repair, senescence, and death

This chapter defines the terms oxidative stress and oxidative damage, and explains how they can affect cell behaviour: proliferation, adaptation, injury, senescence, intercellular communication, and cell death by apoptosis, necrosis, parthanatos (activation of poly-ADP ribose polymerase), and other mechanisms such as pyroptosis. The role played by reactive species (RS) in apoptosis is detailed. The effects of reactive species (RS) on ion channels and ion levels are presented, especially for K+, Ca2+, iron ions, and copper ions. Methods to measure the liberalization of 'catalytic' iron and copper ions by oxidative stress are described. There is a detailed description of the mechanisms by which RS (including hydroxyl radicals, singlet oxygen, hypochlorous acid, and peroxynitrite) cause damage to DNA, how this can lead to mutations, and how cells counter this by repair mechanisms. The ways in which defects in DNA repair raise the risk of cancer development in diseases, such as xeroderma pigmentosum, Lynch syndrome, ataxia telangiectasia, and Cockayne syndrome are presented. Oxidative protein damage and lipid peroxidation are explored in detail, including the mechanisms that cells have evolved to deal with them. The cellular actions of end-products of lipid peroxidation (isoprostanes, aldehydes, cholesterol oxidation products etc.) are reviewed. Heat-shock proteins, the acute phase response, the proteasome, and autophagy are described in detail. Redox regulation in bacterial, yeast and animal cells is reviewed in detail, and its physiological relevance discussed, especially for kinases, phosphatases (including PTEN), Nrf2, NF-κB (particularly the role of ROS in regulating its activity), AP-1, and mitochondria-to-nucleus signalling.