Oxidative stress adaptation with acute,chronic, and repeated stress

Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life.     

Hepatitis C virus, ER stress, and oxidative stress

Hepatitis C virus (HCV) replication is associated with the endoplasmic reticulum (ER), where the virus causes stress. Cells cope with ER stress by activating an adaptive program called the unfolded protein response (UPR), which alleviates this stress by stimulating protein folding and degradation in the ER and down-regulating overall protein synthesis. Recent work suggests that HCV also alters ER calcium homeostasis, inducing oxidative stress. Future progress in understanding the control that HCV exerts over the ER will provide insight into viral strategies for pathogenesis and persistence in chronically infected patients.     

Oxidative stress associated with exercise,psychological stress and life-style factors

Oxidative stress is a cellular or physiological condition of elevated concentrations of reactive oxygen species that cause molecular damage to vital structures and functions. Several factors influence the susceptibility to oxidative stress by affecting the antioxidant status or free oxygen radical generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress.Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress. Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property.     

Oxidative stress,antioxidants and stress tolerance

Traditionally, reactive oxygen intermediates (ROIs) were considered to be toxic by-products of aerobic metabolism, which were disposed of using antioxidants. However, in recent years, it has become apparent that plants actively produce ROIs as signaling molecules to control processes such as programmed cell death, abiotic stress responses, pathogen defense and systemic signaling. Recent advances including microarray studies and the development of mutants with altered ROI-scavenging mechanisms provide new insights into how the steady-state level of ROIs are controlled in cells. In addition, key steps of the signal transduction pathway that senses ROIs in plants have been identified. These raise several intriguing questions about the relationships between ROI signaling, ROI stress and the production and scavenging of ROIs in the different cellular compartments.     

NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis

Endoplasmic reticulum (ER)-induced apoptosis and oxidative stress contribute to several chronic disease processes, yet molecular and cellular mechanisms linking ER stress and oxidative stress in the setting of apoptosis are poorly understood and infrequently explored in vivo. In this paper, we focus on a previously elucidated ER stress-apoptosis pathway whose molecular components have been identified and documented to cause apoptosis in vivo. We now show that nicotinamide adenine dinucleotide phosphate reduced oxidase (NOX) and NOX-mediated oxidative stress are induced by this pathway and that apoptosis is blocked by both genetic deletion of the NOX subunit NOX2 and by the antioxidant N-acetylcysteine. Unexpectedly, NOX and oxidative stress further amplify CCAAT/enhancer binding protein homologous protein (CHOP) induction through activation of the double-stranded RNA-dependent protein kinase (PKR). In vivo, NOX2 deficiency protects ER-stressed mice from renal cell CHOP induction and apoptosis and prevents renal dysfunction. These data provide new insight into how ER stress, oxidative stress, and PKR activation can be integrated to induce apoptosis in a pathophysiologically relevant manner.     

Cheap,cost-effective,and quick stress biomarkers for drought stress detection and monitoring in plants

The detection and monitoring of drought stress in plants growing in their natural habitat are essential for the study of plant stress physiology. However, with the advent of plant phenotyping and new -omics technologies, the application of simple, cheap, cost-effective, quick, and practical methods to assess drought stress in plants seems more challenging than ever, particularly in low-income countries. Here, currently available methods that do not require specialized equipment, but reliably detect and monitor drought stress in plants at low cost will be discussed. This will not only boost research on plant stress physiology in low-income countries but will also help several laboratories with very limited resources around the globe to perform high-quality research.     

Oxidative stress, insulin signaling, and diabetes

Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can arise from a number of different sources, whether disease state or lifestyle, including episodes of ketosis, sleep restriction, and excessive nutrient intake. Oxidative stress activates a series of stress pathways involving a family of serine/threonine kinases, which in turn have a negative effect on insulin signaling. More experimental evidence is needed to pinpoint the mechanisms contributing to insulin resistance in both type 1 diabetics and nondiabetic individuals. Oxidative stress can be reduced by controlling hyperglycemia and calorie intake. Overall, this review outlines various mechanisms that lead to the development of oxidative stress. Intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and the development of diabetes.     

Endoplasmic reticulum stress, obesity and diabetes

The endoplasmic reticulum (ER) stress response, also commonly known as the unfolded protein response (UPR), is an adaptive response used to align ER functional capacity with demand. It is activated in various tissues under conditions related to obesity and type 2 diabetes. Hypothalamic ER stress contributes to inflammation and leptin/insulin resistance. Hepatic ER stress contributes to the development of steatosis and insulin resistance, and components of the UPR regulate liver lipid metabolism. ER stress in enlarged fat tissues induces inflammation and modifies adipokine secretion, and saturated fats cause ER stress in muscle. Finally, prolonged ER stress impairs insulin synthesis and causes pancreatic β cell apoptosis. In this review, we discuss ways in which ER stress operates as a common molecular pathway in the pathogenesis of obesity and diabetes.     

Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes

Oxidative stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a cellular adaptive response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative stress and cellular stress response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic cellular stress response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.     

Oxidative stress, human genetic variation, and disease

Oxidative stress has been implicated in numerous pathophysiological conditions and also aging. The tools for studying oxidative stress are now expanding as a result of the human genome effort and, in particular, expanding knowledge on human genetic variation. A few genetic variants, mostly in the form of single nucleotide polymorphisms of relevance to oxidative stress are already studied by a molecular epidemiologic approach. A review of the current knowledge on variant human genes that are directly implicated in human protection against oxidative stress is presented.     

Alcohol stress,membranes, and chaperones

Ethanol, which affects all body organs, exerts a number of cytotoxic effects, most of them independent of cell type. Ethanol treatment leads to increased membrane fluidity and to changes in membrane protein composition. It can also interact directly with membrane proteins, causing conformational changes and thereby influencing their function. The cytotoxic action may include an increased level of oxidative stress. Heat shock protein molecular chaperones are ubiquitously expressed evolutionarily conserved proteins which serve as critical regulators of cellular homeostasis. Heat shock proteins can be induced by various forms of stresses such as elevated temperature, alcohol treatment, or ischemia, and they are also upregulated in certain pathological conditions. As heat shock and ethanol stress provoke similar responses, it is likely that heat shock protein activation also has a role in the protection of membranes and other cellular components during alcohol stress.     

Elastic moduli, yield stress, and ultimate stress of cancellous bone in the canine proximal femur

Elastic moduli, yield stress and ultimate compressive stress were determined for cancellous bone from the femoral head and neck regions of the canine femur. Unconfined compression tests were performed on 5 mm cubic samples which were cut from two femurs. Elastic moduli were measured in three orthogonal directions, and the yield stress and ultimate stress were measured along the proximal-distal axis. The results from this investigation support previous assumptions that the mechanical behavior of canine cancellous bone is qualitatively similar to human cancellous bone. The canine cancellous bone was observed to be anisotropic in elastic modulus. For two thirds of the cubic specimens tested, the elastic modulus was largest in the load-bearing, proximal-distal direction. A linear relationship between yield stress and elastic modulus was observed for canine bone, as is typical of human bone. A similar linear relationship between ultimate stress and elastic modulus was observed. Thus, for canine bone as well as for human bone, failure appears to be governed by a strain level which is position independent. The yield strain of 0.0259 and ultimate strain of 0.0288 for canine bone were both less than the yield strain of 0.0395 reported for human bone.     

Abiotic stress, the field environment and stress combination

Farmers and breeders have long known that often it is the simultaneous occurrence of several abiotic stresses, rather than a particular stress condition, that is most lethal to crops. Surprisingly, the co-occurrence of different stresses is rarely addressed by molecular biologists that study plant acclimation. Recent studies have revealed that the response of plants to a combination of two different abiotic stresses is unique and cannot be directly extrapolated from the response of plants to each of the different stresses applied individually. Tolerance to a combination of different stress conditions, particularly those that mimic the field environment, should be the focus of future research programs aimed at developing transgenic crops and plants with enhanced tolerance to naturally occurring environmental conditions.     

Cryptococcus neoformans, a fungus under stress

Cryptococcus neoformans is a human fungal pathogen that survives exposure to stresses during growth in the human host, including oxidative and nitrosative stress, high temperature, hypoxia, and nutrient deprivation. There have been many genes implicated in resistance to individual stresses. Notably, the catalases do not have the expected role in resistance to external oxidative stress, but specific peroxidases appear to be critical for resistance to both oxidative and nitrosative stresses. Signal transduction through the HOG1 and calcineurin/calmodulin pathways has been implicated in the stress response. Microarray and proteomic analyses have indicated that the common responses to stress are induction of metabolic and oxidative stress genes, and repression of genes encoding translational machinery.     

P bodies, stress granules, and viral life cycles

Eukaryotic mRNAs are in a dynamic equilibrium between different subcellular locations. Translating mRNAs can be found in polysomes, mRNAs stalled in translation initiation accumulate in stress granules and mRNAs targeted for degradation or translation repression can accumulate in P bodies. Partitioning of mRNAs between polysomes, stress granules, and P bodies affects rates of translation and mRNA degradation. Host proteins within P bodies and stress granules can enhance or limit viral infection, and some viral RNAs and proteins accumulate in P bodies and/or stress granules. Thus, an important interplay among P bodies, stress granules, and viral life cycles is beginning to emerge.     

Exercise,free radicals and oxidative stress

This article reviews the role of free radicals in causing oxidative stress during exercise. High intensity exercise induces oxidative stress and although there is no evidence that this affects sporting performance in the short term, it may have longer term health consequences. The mechanisms of exercise-induced oxidative stress are not well understood. Mitochondria are sometimes considered to be the main source of free radicals, but in vitro studies suggest they may play a more minor role than was first thought. There is a growing acceptance of the importance of haem proteins in inducing oxidative stress. The release of metmyoglobin from damaged muscle is known to cause renal failure in exercise rhabdomyolysis. Furthermore, levels of methaemoglobin increase during high intensity exercise, while levels of antioxidants, such as reduced glutathione, decrease. We suggest that the free-radical-mediated damage caused by the interaction of metmyoglobin and methaemoglobin with peroxides may be an important source of oxidative stress during exercise.     

Habitats,stress, and evolutionary rates

Habitats of organisms are expressed as an interaction between stress intensity, magnitude of environmental fluctuations, and energy availability from resources. Under this model organisms should evolve broad biological properties defined by such physical characteristics. When energy is severely restricted under the continuing constant stress of adversity-selection, or in widely fluctuating and highly stressful environments, little evolutionary change is expected; relict species and ‘living fossils’ are the respective expectations. In rather stable abiotic environments where resources are limited habitat preferences may develop leading to specialization and ultimately adaptive radiations. On the other hand major new innovations are more likely in highly disturbed resource-rich habitats. Evidence from the living and fossil biota is presented which is consistent with these conclusions.     

Adolescent mothers, stress, and prevention

Adolescent mothers face problems that can lead to psychological stress. Based on prospective data from the present study, these problems point toward the need for a coping skills prevention approach to help adolescent mothers manage stress. This paper reports data from outcome research on such an approach with adolescent mothers. Subjects were 79 adolescent mothers who were tested before, immediately after, and three months following the provision of coping skills intervention in an experimental condition. Subjects in a test-only control condition received no special intervention. At posttest, experimental condition subjects showed more positive outcomes on measures of social support, cognitive performance, conflict management, and interpersonal competence. At three-month follow-up, experimental condition subjects had more positive outcomes on social support, cognitive performance, parenting ability, child care self-efficacy, and measures of psychological well-being.