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The new edition of this well-established book is thoroughly revised and gives a comprehensive account of the role of free radicals, other reactive species RS , and antioxidants in life, health, and disease. Free radicals Chemistry -- Physiological effect. View all subjects. User lists Similar Items. Print version: Halliwell, Barry. View PDF. Save to Library. Create Alert. Launch Research Feed. Share This Paper. Citations Publications citing this paper. Oxygen-derived species: their relation to human disease and environmental stress.
More The new edition of this well-established book is thoroughly revised and gives a comprehensive account of the role of free radicals, other reactive species RS , and antioxidants in life, health, and disease. Authors Affiliations are at time of print publication. Gutteridge, author More Less. Print Email Share This. Show Summary Details. Subscriber Login Email Address. Password Please enter your Password.
Library Card Please enter your library card number. View: no detail some detail full detail. Chapter 1 Oxygen: boon yet bane—introducing oxygen toxicity and reactive species. What about H 2 O 2? Knockout of catalase or GPx1 in animals does not cause many problems, but removal of both GPx1 and GPx2 predisposed mice to inflammation and cancer of the intestines, and knockout of GPx4 is embryonic lethal Chu et al.
Knockouts of peroxiredoxins in mice also cause problems anemia, cancer, etc. Indeed, this damage may contribute to the age-related development of cancer in animals Ames, ; Halliwell, and perhaps even to ageing itself.
So why are all the ROS not eliminated? Probably because ROS perform important roles, so the challenge was to evolve antioxidant defenses that allow such roles while minimizing damage. Mechanisms to cope with oxidative damage are required, e. In what ways could ROS be beneficial? Plants provide lots of examples.
ROS production in animals by phagocytes and by other cells in the gastrointestinal and respiratory tracts is a defense against microorganisms Fang, ; Donko et al. Everyone is familiar with regulation of cellular processes by phosphorylation and dephosphorylation of enzymes and transcription factors, but we have realized in the past decade that regulation by oxidation and reduction redox regulation is equally important.
Not only that, the two systems cross talk, i. For example, binding of ligands to growth factor receptors on animal cells activates protein kinases that then phosphorylate and activate subsequent proteins in the signal cascade. Often at the same time, cellular ROS levels increase and facilitate the signaling. Although some kinases can be directly affected by ROS e.
Instead, they increase net phosphorylation by inhibiting protein dephosphorylation Rhee et al. Protein phosphatase enzymes are constantly active in cells, but can be attacked and inactivated by ROS.
Thus, the ligand binding increases kinase activity, and the ROS assist by transiently inactivating phosphatases. Where do the ROS come from? These were originally described in phagocytes Fang, , but are now known to be widespread in animal and plant, see the rest of this issue cells.
In addition, when cells are exposed to extra H 2 O 2 e. The cell then rapidly makes more peroxiredoxin, and reactivates the inactive form, so that the extra H 2 O 2 can be removed after it has done its job Georgiou and Masip, ; Rhee et al. Mitochondrial ROS production is often thought of as a nuisance, an unavoidable consequence of electron leakage under O 2 , a view consistent with the severe phenotype of MnSOD-knockout mice.
However, another view is that variations in mitochondrial H 2 O 2 production are a signal that advises the cytoplasm and nucleus what the mitochondria are doing, leading to changes in nuclear gene transcription via redox regulation and phosphorylation of transcription factors.
Mitochondrially targeted antioxidants are proving useful in attempts to study the physiological roles of mitochondrial ROS Sheu et al. Chloroplast ROS may perform similar roles. What happens if the balance between ROS and antioxidants is upset? Having too many ROS in relation to the available antioxidants is said to be a state of oxidative stress. Sies defined this term as a disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage.
Such damage is often called oxidative damage, which has been defined as the biomolecular damage caused by attack of reactive species upon the constituents of living organisms Halliwell and Whiteman, Increased oxidative damage can result not only from more oxidative stress, but also from failure to repair or replace damaged biomolecules. Oxidative stress can result from decreases in antioxidant levels, e. Depletions of dietary antioxidants and other essential dietary constituents e.
For example, children with the protein deficiency disease kwashiorkor suffer oxidative stress, involving low GSH levels lack of sulfur-containing amino acids in the diet and iron overload inability to make enough transferrin; Fuchs, Oxidative stress can also be due to increased ROS production, e.
What do cells do when under oxidative stress? It depends on the cell and the level of stress applied Fig. Several cell types respond to mild oxidative stress by proliferating, which can be good in wound healing but bad if it leads to tissue fibrosis Cave et al.
This may completely protect against damage, protect against damage to some extent but not completely, or sometimes overprotect; the cells are then resistant to higher levels of oxidative stress imposed subsequently. Adaptation need not always involve increases in antioxidants: there can be decreases in ROS-producing systems, increases in other protective mechanisms such as chaperones , or changes in oxidative damage targets e.
Moderate oxidative stress usually halts the cell cycle, or can drive cells into senescence; the cell survives but can no longer divide. Severe oxidative damage, especially to DNA, may trigger death by apoptosis, necrosis, or mechanisms with features of both. Indeed, ROS act as triggers of apoptosis, and as participants in apoptosis induced by other mechanisms, in both plants and animals.
How cells respond to oxidative stress. Stimulation of proliferation by low levels of reactive species is associated with increased net phosphorylation of multiple proteins.
HO-1, Haem oxygenase 1; RS, reactive species. ROS are all over the place in plants, animals, and aerobic bacteria. We cannot live without them or we will probably die from infections. Yet, they often kill us in the end; over the long human lifespan, the continual damage by ROS, if not properly repaired and repair efficiency tends to drop in the aged can contribute to the age-related development of cancer, neurodegenerative diseases, and many other disorders Ames, ; Halliwell and Gutteridge, This may be a by product of evolution; ROS are essential for defense against infection and signaling, keeping you alive until your reproduction has finished and children have grown up.
Who cares if they kill you in the later postreproductive years? Evolution doesn't. So why does taking antioxidant supplements not make us live healthily for ever? The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors www. National Center for Biotechnology Information , U. Journal List Plant Physiol v.
Plant Physiol. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Photosynthesis: The Ultimate Paradox? Oxygen Toxicity All aerobes including plants, aerobic bacteria, and humans, suffer damage when exposed to O 2 concentrations higher than normal Gilbert, ; Balentine, ; Halliwell and Gutteridge, , signifying that they have no excess of antioxidant defenses.