Showing papers on "Oxidative stress published in 1994"
TL;DR: Thomas Buttke and Paul Sandstrom suggest that eukaryotic cells may benefit from this perilous existence by invoking oxidative stress as a common mediator of apoptosis.
2,204 citations
TL;DR: The cytotoxic action of A beta on neurons results from free radical damage to susceptible cells, suggesting that A beta activates a member of this class of enzymes.
2,060 citations
TL;DR: Transgenic plants offered a means by which to achieve a more complete understanding of the roles of the enzymes involved in protection against stress of many types: environmental and man-made.
Abstract: Free radicals and other active derivatives of oxygen are inevitable by-products of biological redox reactions. Reduced oxygen species, such as hydrogen peroxide, the superoxide radical anion and hydroxyl radicals, inactivate enzymes and damage important cellular components. In addition, singlet oxygen, produced via formation of triplet state chlorophyll, is highly destructive. This oxygen species initiates lipid peroxidation, and produces lipid peroxy radicals and lipid hydroperoxides that are also very reactive. The increased production of toxic oxygen derivatives is considered to be a universal or common feature of stress conditions. Plants and other organisms have evolved a wide range of mechanisms to contend with this problem. The antioxidant defence system of the plant comprises a variety of antioxidant molecules and enzymes. Considerable interest has been focused on the ascorbate-glutathione cycle because it has a central role in protecting the chloroplasts and other cellular compartments from oxidative damage. It is clear that the capacity and activity of the antioxidative defence systems are important in limiting photo-oxidative damage and in destroying active oxygen species that are produced in excess of those normally required for signal transduction or metabolism. In our studies on this system, we became aware that the answers to many unresolved questions concerning the nature and regulation of the antioxidative defence system could not be obtained easily by either a purely physiological or purely biochemical approach. Transgenic plants offered us a means by which to achieve a more complete understanding of the roles of the enzymes involved in protection against stress of many types: environmental and man-made. The ability to engineer plants which express introduced genes at high levels provides an opportunity to manipulate the levels of these enzymes, and hence metabolism in vivo. Studies on transformed plants expressing increased activities of single enzymes of the antioxidative defence system indicate that it is possible to confer a degree of tolerence to stress by this means. However, attempts to increase stress resistance by simply increasing the activity of one of the antioxidant enzymes have not always been successful presumably because of the need for a balanced interaction of protective enzymes. The study of these transformed plants has allowed a more complete understanding of the roles of individual enzymes in metabolism. Protection against oxidative stress has become a feasible objective through the application of molecular genetic techniques in conjunction with a biochemical and physiological approach.
1,261 citations
TL;DR: The most important electron acceptor in the biosphere is molecular oxygen which, by virtue of its bi-radical nature, readily accepts unpaired electrons to give rise to a series of partially reduced species collectively known as reduced (or ‘reactive’) oxygen species (ROS).
Abstract: The most important electron acceptor in the biosphere is molecular oxygen which, by virtue of its bi-radical nature, readily accepts unpaired electrons to give rise to a series of partially reduced species collectively known as reduced (or ‘reactive’) oxygen species (ROS). These include superoxide (O·-2), hydrogen peroxide (H2O2), hydroxyl radical (HO·) and peroxyl (ROO·) and alkoxyl (RO·) radicals which may be involved in the initiation and propagation of free radical chain reactions and which are potentially highly damaging to cells. Mechanisms have evolved to restrict and control such processes, partly by compartmentation, and partly by antioxidant defences such as chain-breaking antioxidant compounds capable forming stable free radicals (e.g. ascorbate, α-tocopherol) and the evolution of enzyme systems (e.g. superoxide dismutase, catalase, peroxidases) that diminish the intracellular concentration of the ROS. Although some ROS perform useful functions, the production of ROS exceeding the ability of th...
1,256 citations
TL;DR: Comparing the efficiency of three different antioxidant enzymes: Cu/Zn-superoxide dismutase, catalase, and selenium-glutathione peroxidase shows that all three antioxidant enzymes give protection for the cells, and emphasizes the fact that each enzyme has a specific as well as an irreplaceable function.
1,156 citations
TL;DR: Observations would suggest that the COMET assay is a useful tool for examining issues related to oxidative stress in human lymphocytes.
Abstract: The effects of antioxidants and various other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes have been investigated using the COMET assay. Hydrogen peroxide (H2O2) and bleomycin (BLM) have produced clear dose-related responses. In 38 independent experiments, there was consistency between the two donors used in the study for the negative and positive control data. The endogenous antioxidant catalase abolished effects with H2O2, but only slightly affected the response with BLM. Superoxide dismutase did not alter the response with H2O2 and only slightly affected BLM. The exogenous antioxidant vitamin C produced a clear dose-related response on its own. In combination with H2O2, there were small protective effects at low doses and exacerbating effects at high doses, but these were within the inter-experimental variability range. Vitamin E (trolox) produced no effects with either H2O2 or BLM, or on its own. Silymarin protected against the effect due to H2O2. Other modifying agents such as apo-transferrin and deferoxamine mesylate produced a clear dose-related protection of effects due to BLM. This protection was less due to H2O2. In the presence of ferrous chloride, the effect due to BLM was exacerbated. In a small sample of 6 smokers and 6 non-smokers, responses from smokers approached borderline significance (P = 0.054) by comparison with non-smokers. These observations would suggest that the COMET assay is a useful tool for examining issues related to oxidative stress in human lymphocytes.
629 citations
TL;DR: Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes, and antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary.
Abstract: Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same.
584 citations
TL;DR: Results indicate that this increase in YAP1‐specific binding to DNA is not due to an increase in synthesis of Yap1 protein, but rather results from modification of pre‐existing protein.
Abstract: The role of the YAP1 transcription factor in the response of Saccharomyces cerevisiae cells to a variety of conditions that induce oxidative stress has been investigated. Cells deficient in YAP1 were found to be hypersensitive to hydroperoxides and thioloxidants, whereas overexpression of YAP1 conferred hyper-resistance to the same conditions. These treatments resulted in an increase in YAP1-specific binding to DNA together with an increase in YAP1 dependent transcription. Our results indicate that this increase is not due to an increase in synthesis of YAP1 protein, but rather results from modification of pre-existing protein. Using a specific genetic screen, the TRX2 gene, one of two genes of S. cerevisiae that encode thioredoxin protein, was identified as being essential for YAP1 dependent resistance to hydroperoxides. Furthermore, efficient expression of TRX2 was dependent on YAP1 and enhanced under conditions of oxidative stress.
475 citations
425 citations
TL;DR: The cumulative effects of oxidative stress on diabetic endothelial cell dysfunction, together with the complex interrelationship of cyclooxygenase catalysis, protein kinase C activity, and flux through the polyol pathway, are considered.
405 citations
TL;DR: Their increased production seems to accompany most forms of tissue injury, and the formation of free radicals has been implicated in a multitude of disease states ranging from inflammatory/immune injury to myocardial infarction and cancer.
Abstract: The occurrence of reactive oxygen species (ROS), termed as prooxidants, is a characteristic of normal aerobic organisms. The term “reactive oxygen species” collectively denotes oxygen-centered radicals such as superoxide (O2·-)and hydroxyl (·OH), as well as nonradical species derived from oxygen, such as hydrogen peroxide (H2O2), singlet oxygen (1ΔgO2) and hypochlorous acid (HOC1). Radical reactions are central to the maintenance of homeostasis in biological systems. Radical species perform a cardinal role in many physiological processes such as cytochrome P450-mediated oxidative transformation reactions, a plethora of enzymic oxidation reactions, oxidative phosphorylation, regulation of the tone of smooth muscle, and killing of microorganisms.1–3 Excessive generation of free radicals can have deleterious biological consequences.4–6 Organisms are equipped with an armamentarium of defense systems, termed antioxidants in order to safeguard them against the onslaught of ROS.1–3,7 When the generation of prooxidants overwhelms the capacity of antioxidant defense systems oxidative stress ensues. This can cause tissue damage leading to pathophysiological events. ROS play a pivotal role in the action of numerous foreign compounds (xenobiotics). Their increased production seems to accompany most forms of tissue injury.4,5 Whether sustained and increased production of ROS is a primary event in human disease progression or a secondary consequence of tissue injury has been discussed.5,6 Whatever may be the case, the formation of free radicals has been implicated in a multitude of disease states ranging from inflammatory/immune injury to myocardial infarction and cancer.
TL;DR: Free radicals, their reactive intermediates, low molecular weight aldehyde byproducts derived from lipid peroxidation and antioxidant status are important measurements the authors can utilize to provide a more comprehensive understanding of pathologic mechanisms.
Abstract: It is almost impossible to read through a medical journal, or even the newspaper and not encounter an article that deals with oxidative stress, or with antioxidant involvement in a disease process. Indeed, free radicals, their reactive intermediates, low molecular weight aldehyde byproducts derived from lipid peroxidation and antioxidant status are important measurements we can utilize to provide a more comprehensive understanding of pathologic mechanisms (1–8). All subcellular organelles normally generate superoxide (O2·-), hydrogen peroxide and a variety of free radicals ie; hydroyl (OH·), perhydroxy(HO2·), carbon and nitrogen centered. It has been estimated that 10 billion of these radicals are produced daily via autoxidation and metabolic reactions. In cellular injury, increased amounts of O2·- radicals and peroxides can arise from the mitochondrial electron-transport system during hypoxia and following reperfusion, they can arise primarily through the activation of NADPH oxidase in phagocyte plasma membranes or from platelet derived endoperoxides of arachidonic acid, from the conversion of xanthine dehydrogenase to xanthine oxidase in tissue and from the generation of OH· radicals in iron-catalyzed reactions involving hemoproteins (9). The most current review by Chaudiere covers theoretical and factual site-specific formation and damage (10).
TL;DR: The hypothesis that oxidative damage to long-lived post-mitotic cells may be a key factor in the aging process is supported, as the DR-related amelioration of DNA oxidative damage was greater in the post-Mitotic tissues compared to those undergoing slow mitoses.
TL;DR: In this paper, the redox cycling quinone, 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), was shown to stimulate growth, triggered apoptosis, or caused necrosis of pancreatic RINm5F cells, depending on the dose and duration of the exposure.
TL;DR: The results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma G CS-HS gene and the subsequent elevation in gamma GCS activity.
TL;DR: The proposal that the induction of heme oxygenase by cobalt chloride may be a general response to oxidant stress and, by increasing bilirubin levels, could constitute an important cellular defense mechanism against oxidative damage is supported.
TL;DR: Results suggest that protection provided by N-acetylcysteine and buthionine sulfoximine derives from shunting of the amino acid cysteine from global protein synthesis into the formation of the antioxidant glutathione.
Abstract: Although macromolecular synthesis inhibitors have been demonstrated to prevent neuronal apoptosis in a number of paradigms, their mechanisms of protection remains unclear. Recently, we found that neuronal death resulting from cystine deprivation, glutathione loss, and oxidative stress is apoptotic and is prevented by inhibitors of macromolecular synthesis. We now report that protection is associated with enhanced availability of acid-soluble cyst(e)ine and restoration of cellular glutathione levels. N-acetylcysteine, an agent that delivers exogenous cysteine intracellularly and raises glutathione, is also protective, while buthionine sulfoximine, an inhibitor of glutathione synthesis, prevents protection by inhibitors of macromolecular synthesis. These results suggest that protection provided by these agents, in this paradigm, derives from shunting of the amino acid cysteine from global protein synthesis into the formation of the antioxidant glutathione.
TL;DR: The lipid peroxides thereby generated exhibit powerful negative correlations with the movement characteristics of the spermatozoa and their capacity for sperm-oocyte fusion should have important implications for the development of rational techniques for the diagnosis and treatment of male infertility.
Abstract: There is a growing body of evidence to indicate that a significant factor in the aetiology of male infertility involves a loss of sperm function as a consequence of oxidative stress. This stress originates from the excessive generation of reactive oxygen species by the spermatozoa and results in the peroxidation of unsaturated fatty acids in the sperm plasma membrane. It is possible that reactive oxygen species originating from infiltrating leucocytes could also stress the spermatozoa although the protective properties of seminal plasma would render this unlikely in vivo. Whatever the source of the reactive oxygen species, the lipid peroxides thereby generated exhibit powerful negative correlations with the movement characteristics of the spermatozoa and their capacity for sperm-oocyte fusion. These findings should have important implications for the development of rational techniques for the diagnosis and treatment of male infertility.
01 Jan 1994
TL;DR: Part 1 Chemical and biochemical aspects: chemistry of iron and copper in radical reactions, W.H. Koppenol some chemical and biochemical constraints of oxidative stress in living cells, and pathological aspects: therapeutic iron chelating-agents and free radical pathways in the inflammatory response.
Abstract: Part 1 Chemical and biochemical aspects: chemistry of iron and copper in radical reactions, W.H. Koppenol some chemical and biochemical constraints of oxidative stress in living cells, J. Chaudiere ferryl iron and protein free radicals, C.E. Cooper antioxidants and free radical scavengers, A.T. Diplock formation of free radicals and mechanisms of action in normal biochemical processes and pathological states, C.A. Rice-Evans free radicals and cell proliferation, R.H. Burdon. Part 2 Pathological aspects: therapeutic iron chelating-agents, S. Singh and R.C. Hider free radicals in central nervous system injury, E.D. Hall ultraviolet radiation, (UVA, UVB) and skin antioxidants, L. Packer free radicals and atherosclerosis, J.C. Fruchart and P. Duriez chemical aspects of free radical reactions in connective tissue, B.J. Parsons free radicals and connective tissue damage, M.S. Baker free radicals in toxicology with an emphasis on electron spin resonance investigations, R.P. Mason and C.F. Chignell radical generation and detection in myocardial injury, B. Kalyanaraman et al free radical pathways in the inflammatory response, P.G. Winyard et al.
TL;DR: An improved understanding of the mechanism by which reducing equivalents are supplied by tissues to respond to an oxidative stress may direct future research toward designing strategies for augmenting the ability of tissues to defend themselves against oxidative stress induced by reperfusion or xenobiotics.
TL;DR: Structural-activity analysis suggests that gallic acid induces apoptosis in HL-60RG cells, depending on its distinctive feature derived from the structure but not on its antioxidative activity.
TL;DR: The results indicated that chilling, in general, impairs respiratory activity, the cytochrome pathway of electron transport, and ATPase activity regardless of the treatment and that chilling-induced oxidative stress seems to be a factor for causing possible irreversible damage to the mitochondrial membrance components.
Abstract: Our previous results indicated that 3-d-old dark-grown chilling-sensitive maize (Zea mays L.) seedlings did not survive 7 d of 4[deg]C chilling stress, but 69% of them survived similar stress when the seedlings were either preexposed to 14[deg]C for 3 d or pretreated with 0.1 mM H2O2 for 4 h at 27[deg]C (T.K. Prasad, M.D. Anderson, B.A. Martin, C.R. Stewart [1994] Plant Cell 6: 65-74) or 1 mM abscisic acid (ABA) for 24 h at 27[deg]C (M.D. Anderson, T.K. Prasad, B.A. Martin, C.R. Stewart [1994] Plant Physiol 105: 331-339). We discovered that chilling imposed oxidative stress on the seedlings. Since H2O2 accumulated during the periods of both acclimation and nonacclimation, we concluded that H2O2 had dual effects at low temperature: (a) During acclimation, its early transient accumulation signals the induction of antioxidant enzymes such as catalase 3 and peroxidase to scavenge H2O2; and (b) at 4[deg]C in nonacclimated seedlings, it accumulates to damaging levels in the tissues because of low levels of these and perhaps other antioxidant enzymes. Three-day-old seedlings pretreated with H2O2 (a mild oxidative stress) or ABA showed induced chilling tolerance. In the present study, we investigated whether mitochondria are a target for chilling-induced oxidative stress and, if so, what differences do acclimation, H2O2, or ABA make to protect mitochondria from irreversible chilling injury. The results indicated that chilling, in general, impairs respiratory activity, the cytochrome pathway of electron transport, and ATPase activity regardless of the treatment. In pretreated seedlings, the activities of catalase 3 and peroxidase in the mitochondria increased severalfold compared with control and nonacclimated seedlings. The increases in these antioxidant enzymes imply that mitochondria are under oxidative stress and such increases could initiate a protective mechanism in the mitochondria. Mitochondrial respiration is partially cyanide resistant during chilling stress and also after the 1st d of recovery. Upon further recovery over 3 d, in contrast to nonacclimated seedlings, the mitochondria of acclimation-, H2O2-, and ABA-treated seedlings showed the following recovery features. (a) The mitochondrial respiration changed from a cyanide-resistant to a cyanide-sensitive cytochrome pathway, (b) cytochrome oxidase activity recovered to control levels, (c) the ability of mitochondria to generate ATP was regained, and (d) the antioxidant enzyme activities remained at or above control levels. Based on these results, we conclude that chilling impairs mitochondrial function and that chilling-induced oxidative stress seems to be a factor, at least in part, for causing possible irreversible damage to the mitochondrial membrance components. Acclimation, H2O2, and ABA provide a protective mechanism by inducing antioxidant enzymes to protect mitochondria from irreversible oxidative damage that is absent in nonacclimated seedlings. Therefore, we conclude that the ability of the seedlings to recover from chilling injury is, at least in part, due to the ability of the mitochondria to resume normal function.
TL;DR: The results indicate that oxidative stress induces apoptosis in thymocytes, and this induction can be prevented by Trolox, a powerful inhibitor of membrane damage.
TL;DR: The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation.
Abstract: Following the pioneer report of Di Luzio (Physiologist 6, 169-173, 1963) concerning the prevention of the acute ethanol-induced fatty liver by antioxidants, many observations have shown that ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. The disturbances induced in the major hepatic enzymatic and non-enzymatic antioxidant systems following experimental acute and chronic ethanol administration are reviewed, emphasizing the important role of dietary alpha-tocopherol in modifying the induction of oxidative stress and its usual expression as increased lipid peroxidation. Adaptative increases in some elements of the hepatic antioxidant defence partly counteract the enhanced generation of prooxidant free radicals following chronic ethanol intake. By contrast, lipid peroxidation is favoured when ethanol is administered together with a fat-rich diet and/or various xenobiotics. Chronic ethanol feeding has also been reported to potentiate the oxidative stress resulting from an acute ethanol load. By generating potent chemoattractants for human neutrophils and/or by stimulating the expression of genes involved in collagen biosynthesis, liver lipid peroxidation may play an important role in the progression of steatosis to hepatitis and cirrhosis. Oxidative stress has been shown not to be restricted to the liver, but also to affect, under some experimental conditions of ethanol administration, extrahepatic tissues, such as the central nervous system, the heart and the testes. This stress can be partly prevented by vitamin E supplementation. Ethanol-induced antioxidant disturbances have also been reported in clinical studies in blood and liver biopsies. Pharmacological antioxidants could have beneficial effects in reducing the incidence of ethanol-induced changes in cellular lipids, proteins and nucleic acids. The antioxidants considered could act by reducing free radical production (e.g. chelators of redox-active iron derivatives), trapping free radicals themselves, interrupting the peroxidation process or reinforcing the natural antioxidant defence.
TL;DR: The results suggest that in airways the initial response to oxidative stress may be to induce NF k B-responsive genes, such as iNOS, which may play an important role in defending the airway against oxidative stress.
TL;DR: The data suggest that F2-isoprostanes are useful markers of LDL oxidation in vivo, and their formation in LDL demonstrated here may also have important implications for the etiology of cardiovascular disease.
Abstract: F2-isoprostanes are prostaglandin F2-like compounds that are known to be formed in vivo by free radical oxidation of arachidonyl-containing lipids, and their plasma levels have been suggested as indicators of in vivo oxidative stress. As oxidation of LDL, a likely causal factor in atherosclerosis, involves lipid peroxidation, we investigated whether F2-isoprostanes are formed in plasma and LDL exposed to oxidative stress, and how F2-isoprostane formation is related to endogenous antioxidant status. In plasma exposed to aqueous peroxyl radicals, lipid hydroperoxides and esterified F2-isoprostanes were formed simultaneously after endogenous ascorbate and ubiquinol-10 had been exhausted, despite the continued presence of urate, alpha-tocopherol, beta-carotene, and lycopene. In isolated LDL exposed to aqueous peroxyl radicals or Cu2+, consumption of endogenous ubiquinol-10 and alpha-tocopherol was followed by rapid formation and subsequent breakdown of lipid hydroperoxides and esterified F2-isoprostanes, and a continuous increase in LDL's electronegativity, indicative of atherogenic modification. In Cu(2+)-exposed LDL, the decrease in esterified F2-isoprostane levels was paralleled by the appearance of free F2-isoprostanes, suggesting that hydrolysis by an LDL-associated activity had occurred. Our data suggest that F2-isoprostanes are useful markers of LDL oxidation in vivo. As F2-isoprostanes are potent vasoconstrictors and can modulate platelet aggregation, their formation in LDL demonstrated here may also have important implications for the etiology of cardiovascular disease.
TL;DR: The observation that certain thiol antioxidants such as NAC and glutathione can completely block the activation induced death of T cell hybridomas implicates redox regulation in this process.
Abstract: N-Acetylcysteine (NAC) is a well established thiol antioxidant which, after uptake, deacylation and conversion to glutathione functions as both a redox buffer and a reactive oxygen intermediate scavenger. We report here that NAC completely blocks activation induced death and associated DNA fragmentation of myelin basic protein (MBP) specific T cell hybridomas. Conversely, NAC had very little effect on the antigen driven proliferation of a MBP specific T cell line similar to that from which the hybridomas were derived. NAC displayed an analogous absolute inhibition of mitogen mediated activation induced death, even if added up to 3 h post activation. Although glutathione was as efficient as NAC at blocking activation induced death, dithiothreitol displayed minimal inhibition while L-cysteine had no effect at all. The observation that certain thiol antioxidants such as NAC and glutathione can completely block the activation induced death of T cell hybridomas implicates redox regulation in this process.
TL;DR: Results provide strong evidence for the role of inflammatory mediators inducible by oxidative stress in atherogenesis and suggest that a major gene contributing to aortic lesion development in this mouse model, designated Ath-1, may control either the accumulation of lipid peroxides in tissues or the cellular responses to such lipidperoxides.
Abstract: In a previous survey of inbred mouse strains on an atherogenic diet, we observed that the susceptibility to aortic atherosclerotic lesion formation was associated with the accumulation of lipid peroxidation products, induction of inflammatory genes, and the activation of NF-kB-like transcription factors (Liao, F., A. Andalibi, F. C. deBeer, A. M. Fogelman, and A.J. Lusis. 1993. J. Clin. Invest. 91:2572-2579). We hypothesized that the inflammation-related processes were stimulated by oxidized lipids, since injection of minimally oxidized LDL (MM-LDL) activated the same set of genes. We now report that the induction of inflammatory genes and activation of NF-kB-like transcription factors cosegregate with aortic atherosclerotic lesion formation in BXH recombinant inbred strains derived from parental C57BL/6J (susceptible) and C3H/HeJ (resistant) mice. In addition, the accumulation of hepatic conjugated dienes exhibited a significant correlation with inflammatory gene activation. These results provide strong evidence for the role of inflammatory mediators inducible by oxidative stress in atherogenesis. They also suggest that a major gene contributing to aortic lesion development in this mouse model, designated Ath-1, may control either the accumulation of lipid peroxides in tissues or the cellular responses to such lipid peroxides.