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Depressed growth of Morris hepatomas in altitude- and heat-stressed but not in cold-stressed buffalo rats.

Female inbred BUF rats bearing Morris hepatomas 5123C, 5123D, 7795, and 7800 bilaterally in the femoral musculature were exposed for 3 weeks to ether 4,500-m simulated altitude or sea level or to an ambient temperature of either 7, 23, or 33 degrees C. Rats were given inoculations 12 days before these exposures. Tumor size, body weight, food consumption, and body temperatures were measured weekly in these treated rats and in normal rats. At time of killing, tumor mass, DNA synthesis (by [3H]thymidine incorporation), and respiration (by conversion of [1,4-14C]succinic acid to 14CO2) were measured in each of the 4 hepatoma lines, in the livers of normal and host rats, and in regenerated livers 10 days post 70% hepatectomy. Growths of all 4 tumors and regenerated livers were significantly impaired in rats stressed by exposure to altitude and heat but not to cold. Neither DNA synthesis nor respiration was altered in the hepatomas and livers by any environmental stress. The environmentally stressed rats gained weight at a slower rate and consumed less food than did their controls, but no differences were found in these variables for tumor-bearing and non-tumor-bearing rats. However, whereas the ratio of body weight gain to food consumed was reduced under the three stressful environments, that of tumor weight gain to food consumed was not altered by any environment. Host survivorship was not influenced by any of these effects.

Altitude↗

Arbuscular mycorrhizal influence on leaf water potential, solute accumulation, and oxidative stress in soybean plants subjected to drought stress.

This study investigated several aspects related to drought tolerance in arbuscular mycorrhizal (AM) soybean plants. The investigation included both shoot and root tissues in order to reveal the preferred target tissue for AM effects against drought stress. Non-AM and AM soybean plants were grown under well-watered or drought-stressed conditions, and leaf water status, solute accumulation, oxidative damage to lipids, and other parameters were determined. Results showed that AM plants were protected against drought, as shown by their significantly higher shoot-biomass production. The leaf water potential was also higher in stressed AM plants (-1.9 MPa) than in non-AM plants (-2.5 MPa). The AM roots had accumulated more proline than non-AM roots, while the opposite was observed in shoots. Lipid peroxides were 55% lower in shoots of droughted AM plants than in droughted non-AM plants. Since there was no correlation between the lower oxidative damage to lipids in AM plants and the activity of antioxidant enzymes, it seems that first the AM symbiosis enhanced osmotic adjustment in roots, which could contribute to maintaining a water potential gradient favourable to the water entrance from soil into the roots. This enabled higher leaf water potential in AM plants during drought and kept the plants protected against oxidative stress, and these cumulative effects increased the plant tolerance to drought.

Biomass↗

Enhancement of stress-induced synthesis of stress proteins by mastoparan in C6 rat glioma cells.

The levels of two small stress proteins, hsp27 and alpha B crystallin, were low in C6 glioma cells confluency. However, the levels of the two proteins increased after exposure of cells to heat (42 degrees C for 30 min) or arsenite (50-100 microM for 1 h) stress. When cells were exposed to arsenite or heat in the presence of mastoparan, a peptide toxin from wasp venom, the induction of hsp27 and alpha B crystallin was markedly stimulated, as detected by means of specific immunoassays, Western blot analysis, and Northern blot analysis. The response of hsp70 to each stress was also enhanced in the presence of mastoparan. Treatment of cells with 40 microM mastoparan alone barely induced the accumulation of hsp27 and alpha B crystallin. The stimulatory effect of mastoparan was little affected in cells that had been treated with pertussis toxin, but it was strongly suppressed in the presence of quinacrine, an inhibitor of phospholipase A2. These results suggest that mastoparan, which is an activator of phospholipase A2, enhances the responses to stress of hsp27, alpha B crystallin and hsp70 by increasing the metabolic activity of the arachidonic acid cascade.

Animals↗

Modulation of the stress-induced synthesis of stress proteins by a phorbol ester and okadaic acid.

The expression of alphaB crystallin, hsp27, and hsp70 in C6 cells increased when they were exposed to arsenite (50 microM for 1 h) or heat (42 degrees C for 30 min), as detected by specific immunoassays, Western blot analysis, and Northern blot analysis. When cells were exposed to arsenite in the presence of 0.1 microM phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, or 0.2 microM okadaic acid, an inhibitor of phosphoserine/phosphothreonine protein phosphatases, expression of alphaB crystallin was markedly enhanced. The induction of hsp27 and hosp70 expression was also stimulated to a considerable extent in the same cells. The stimulatory effect of PMA was further enhanced in the presence of okadaic acid, but it was strongly inhibited in the presence of 0.5 microM staurosporine, an inhibitor of protein kinase C. PMA and okadaic acid also stimulated the response to heat stress of the expression of alphaB crystallin, but they barely stimulated the response to heat stress of hsp27. The extent of stimulation of the arsenite-induced responses by PMA and okadaic acid was greater when the concentration of arsenite (i.e. the magnitude of the stress) was relatively low (25-50 microM). The arsenite-induced release of arachidonic acid from cells was also stimulated in the presence of PMA and/or akadaic acid, and the stimulatory effects of PMA and okadaic acid on the arsenite-induced accumulation of alphaB crystallin and hsp27 were strongly suppressed by quinacrine, an inhibitor of phospholipase A2. These results suggest that the stimulatory effects of PMA and okadaicacid on the stress responses are cuased, in part, by the increased metabolic activity of the arachidonic acid cascade, as a consequence of the activation of phospholipase A.

Alkaloids↗

Acute stress and re-exposure to the stressful context suppress spontaneous unit activity in the basolateral amygdala via NMDA receptor activation.

Exposure to an acute stressor of intermittent tail-shocks enhances acquisition of the classically conditioned eyeblink response and the enhancement is dependent on NMDA receptor activation in the basolateral nucleus of the amygdala. In the present study, multiple units (spikes/s) were recorded from the basolateral amygdala in response to the stressor of intermittent tailshocks (thirty, 1 mA, 1 s, 1/min) and upon re-exposure to the context in which the stress was administered. Exposure to the stressor suppressed multiple unit activity in the basolateral/lateral amygdala (67% of baseline) which, in some cases, persisted for 48 h after stressor cessation. Re-exposure to the stressful context reactivated the suppression in unit activity (69% of baseline). In a second experiment, it was determined that the stress-induced suppression of neuronal activity was prevented by NMDA receptor antagonism during stressor exposure. It is proposed that the stress-induced suppression of background unit activity enhances the neural representation of environmental cues by enhancing their signal/background noise ratio and thereby facilitates the formation of associations between those cues.

2-Amino-5-phosphonovalerate↗

Stress-related illnesses and sources of stress: comparing M.D.-Ph.D., M.D., and Ph.D. students.

A study was conducted to determine the prevalence and incidence of stress-associated illnesses and to identify possible sources of stress among students enrolled in the M.D.-Ph.D. program of a midwestern university. Specially constructed questionnaires were completed by 45 M.D.-Ph.D. students, 334 M.D. students, and 42 Ph.D. students at this university. The information obtained from the M.D.-Ph.D. students was compared with the responses of the M.D. students and the Ph.D. students. Male M.D.-Ph.D. students had a significantly higher incidence of hypertension, colitis, and asthma, while female M.D.-Ph.D. students reported a higher usage of antacids and occurrence of gastritis or ulcers during the time that they were enrolled in their programs. M.D.-Ph.D. students indicated that the fear of flunking out of school and the grading system were more stressful than did the M.D. students. Additionally, relationship with the graduate adviser and the graduate committee was more stressful to M.D.-Ph.D. students than to Ph.D. students.

Amenorrhea↗

Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit.

Stress-related mucosal disease develops in patients in the intensive care unit and can result in clinically important bleeding, which is associated with increased mortality. Patients in the intensive care unit without either mechanical ventilation or coagulopathy, which are the primary risk factors for such bleeding, do not seem to need or to benefit from prophylactic acid suppression for stress-related mucosal disease. Although histamine-2-receptor antagonists significantly reduce clinically important bleeding in patients in the intensive care unit and are widely used for prophylaxis, their benefits are limited by the rapid development of tolerance. Previous data suggested that agents that elevate the intragastric pH may increase the susceptibility of patients in the intensive care unit to nosocomial pneumonia. However, the largest study to date showed that intravenous histamine-2-receptor antagonists may not significantly increase the risk of ventilator-associated pneumonia or mortality compared with sucralfate, an agent that does not affect intragastric pH. Intravenous proton pump inhibitors are more potent and longer-acting inhibitors of gastric acid production than intravenous histamine-2-receptor antagonists. The ability of proton pump inhibitors to prevent stress-related mucosal disease and clinically important bleeding seems to be clinically meaningful. Preliminary findings have shown that intermittent administration of intravenous pantoprazole, the first proton pump inhibitor available by this route in the United States, is as effective in raising intragastric pH on the first day as a continuous infusion of a histamine-2-receptor antagonist in clinical trials conducted within an intensive care unit setting. This suggests that for stress ulcer prophylaxis, intermittent dosing with an intravenous proton pump inhibitor may be an alternative to high-dose continuous infusions of a histamine-2-receptor antagonist. These agents must be compared in clinical trials conducted in an intensive care unit setting.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Reported stress of parents of burned children differs on the Spanish and English versions of the parenting stress inventory.

The Parenting Stress Inventory (PSI) is a 101-item self-report questionnaire measuring stress in children and their parents. For several years, we have been administering the English and Spanish versions of the PSI to parents of children with >40% total body surface area burn at discharge, 6 months, 1 year, and every year at followup at clinic. The aim of the present study was to evaluate differences between Spanish- and English-speaking families with respect to stress and to further examine potential psychometric differences between the instruments that may contribute to these differences. In the present study, we found the instruments to be equivalent but have significant differences between the two versions, suggesting cultural differences in how coping and stress are manifested in these groups. Spanish-speaking parents noted significantly more distress than the English-speaking parents. Both groups indicated most severe problems on the Child domains of the PSI, suggesting that parents perceived their interactions and relationship as it pertain to their child to be most troubled.

Adaptation, Psychological↗

Protective role of trehalose during severe oxidative stress caused by hydrogen peroxide and the adaptive oxidative stress response in Candida albicans.

The cellular response to the oxidative stress caused by hydrogen peroxide and its putative correlation with the stress protector trehalose was investigated in Candida albicans CAI.4 and the tps1/tps1 double mutant, which is deficient in trehalose synthesis. When exponential wild-type blastoconidia were exposed to high concentrations of hydrogen peroxide, they displayed a high cell survival, accompanied by a marked rise of intracellular trehalose. The latter is due to a moderate activation of trehalose synthase and the concomitant inactivation of neutral trehalase. Identical challenge in the tps1/tps1 double mutant severely reduced cell viability, a phenotype which was suppressed by overexpression of the TPS1 gene. Pretreatment of growing cultures from both strains with either a low, non-lethal concentration of H(2)O(2) (0.5 mM) or a preincubation at 37 degrees C, induced an adaptive response that protected cells from being killed by a subsequent exposure to oxidative stress. During these mild oxidative preincubations, trehalose was not induced in CAI.4 cells and remained undetectable in their tps1/tps1 counterpart. Blastoconidia from the two strains exhibited a similar degree of cell protection during the adaptive response. The induction of trehalose accumulation by H(2)O(2) was not due to an increased expression of TPS1 mRNA. These results are consistent with a mainly protective role of trehalose in C. albicans during direct oxidative stress but not during acquired oxidative tolerance.

Candida albicans↗

Autonomic responsiveness in stress-sensitive and stress-resistant pigs.

The responsiveness of the autonomic nervous system was studied in twenty-six 140 day old thiopentone anaesthetized lean stress-sensitive Pietrain (P) and fatter stress-resistant Gloucester (G) pigs, using the Valsalva like manoeuvre (VLM), and the i.v. tyramine, noradrenaline (NA) and phenylephrine tests. The heart rate responses to the VLM and tyramine tests were greater in P. The pressor response to NA was lower in P, and the change in heart rate per unit change in blood pressure-during phenylephrine infusion was the same in the two breeds. The sympathetic nervous system in P was, therefore, more responsive than that in G, and this was attributable to a higher pre-adrenoreceptor responsiveness in P. The potentially greater sympathetic responsiveness in stress-sensitive pigs could account for their greater leanness, their stress-induced metabolic acidosis, and for their susceptibility to myocardial failure.

Animals↗

Reliability of the urethral closure pressure profile during stress in the diagnosis of genuine stress incontinence.

Urethral pressure profile (UPP) measurements were recorded during stress using the method of Brown and Wickham in 981 patients with lower urinary tract symptoms. This procedure was used to identify patients with genuine stress incontinence (GSI). A clinical stress test in the supine and erect position served to confirm urinary leakage. GSI was diagnosed in 661 patients. (67%), whereas no incontinence was demonstrable in 320 (33%). UPP during stress has a high sensitivity (93.3%) and specificity (82.5%). Compared with other urodynamic investigations, the ease with which it can be performed at the same time as other urodynamic procedures makes a reliable diagnostic adjunct in the assessment of patients with GSI.

Cough↗

Stress remodeling and stress fracture of the humerus in four standardbred racehorses.

Two 2-year-old pacers, a 3-year-old pacer and a 2-year-old-trotter with acute forelimb lameness were admitted for nuclear scintigraphic examination. Horses were grade 3-4/5 lame. There was increased radiopharmaceutical uptake (IRU) in the distal cranial medial aspect of the humerus in one horse and along the caudal humeral cortex in the other three horses. Two of the four horses were affected bilaterally. Radiographic abnormalities consisted of thickening of the caudal cortex of the mid-diaphysis of the humerus but radiographic changes were not present in all horses. All horses were managed with stall rest initially then stall rest with hand-walking followed by limited turn out for a total of four months. None of the horses had raced before injury. One horse has returned to race training and the other three horses have returned to racing. Average time to return to racing was 329 days. Humeral stress fractures in Standardbred horses are rare. Diffuse patterns of IRU have not been reported in the humerus and are likely indicative of severe stress remodeling. Standardbred racehorses with stress fractures or stress remodeling of the humerus appear to have a good prognosis for return to racing.

Animals↗

Oxidative stress and apoptotic events during thermal stress in the symbiotic sea anemone, Anemonia viridis.

Symbiosis between cnidarian and photosynthetic protists is widely distributed over temperate and tropical seas. These symbioses can periodically breakdown, a phenomenon known as cnidarian bleaching. This event can be irreversible for some associations subjected to acute and/or prolonged environmental disturbances, and leads to the death of the animal host. During bleaching, oxidative stress has been described previously as acting at molecular level and apoptosis is suggested to be one of the mechanisms involved. We focused our study on the role of apoptosis in bleaching via oxidative stress in the association between the sea anemone Anemonia viridis and the dinoflagellates Symbiodinium species. Characterization of caspase-like enzymes were conducted at the biochemical and molecular level to confirm the presence of a caspase-dependent apoptotic phenomenon in the cnidarian host. We provide evidence of oxidative stress followed by induction of caspase-like activity in animal host cells after an elevated temperature stress, suggesting the concomitant action of these components in bleaching.

Amino Acid Sequence↗

Perceived stress and stress projected into the spontaneous storytelling of two groups of fourth grade children.

The purpose of this descriptive correlation study was to describe stress levels in fourth grade children from two geographic locations: an inner city recreation club and a suburban parochial school. The use of spontaneous storytelling and a life events questionnaire provided information about the stress being experienced by the children. This article presents story themes and stressful life events of interest to adult caregivers helping children cope with stressful experiences.

Adaptation, Psychological↗

Oxidative stress and stress signaling: menace of diabetic cardiomyopathy.

Cardiovascular disease is the most common cause of death in the diabetic population and is currently one of the leading causes of death in the United States and other industrialized countries. The health care expenses associated with cardiovascular disease are staggering, reaching more than 350 billion dollars in 2003. The risk factors for cardiovascular disease include high fat/cholesterol levels, alcoholism, smoking, genetics, environmental factors and hypertension, which are commonly used to gauge an individual's risk of cardiovascular disease and to track their progress during therapy. Most recently, these factors have become important in the early prevention of cardiovascular diseases. Oxidative stress, the imbalance between reactive oxygen species production and breakdown by endogenous antioxidants, has been implicated in the onset and progression of cardiovascular diseases such as congestive heart failure and diabetes-associated heart dysfunction (diabetic cardiomyopathy). Antioxidant therapy has shown promise in preventing the development of diabetic heart complications. This review focuses on recent advances in oxidative stress theory and antioxidant therapy in diabetic cardiomyopathy, with an emphasis on the stress signaling pathways hypothesized to be involved. Many of these stress signaling pathways lead to activation of reactive oxygen species, major players in the development and progression of diabetic cardiomyopathy.

Antioxidants↗

Differential roles of the universal stress proteins of Escherichia coli in oxidative stress resistance, adhesion, and motility.

The universal stress protein (UspA) superfamily encompasses a conserved group of proteins that are found in bacteria, archaea, and eukaryotes. Escherichia coli harbors six usp genes--uspA, -C, -D, -E, -F, and -G--the expression of which is triggered by a large variety of environmental insults. The uspA gene is important for survival during cellular growth arrest, but the exact physiological role of the Usp proteins is not known. In this work we have performed phenotypic characterization of mutants with deletions of the six different usp genes. We report on hitherto unknown functions of these genes linked to motility, adhesion, and oxidative stress resistance, and we show that usp functions are both overlapping and distinct. Both UspA and UspD are required in the defense against superoxide-generating agents, and UspD appears also important in controlling intracellular levels of iron. In contrast, UspC is not involved in stress resistance or iron metabolism but is essential, like UspE, for cellular motility. Electron microscopy demonstrates that uspC and uspE mutants are devoid of flagella. In addition, the function of the uspC and uspE genes is linked to cell adhesion, measured as FimH-mediated agglutination of yeast cells. While the UspC and UspE proteins promote motility at the expense of adhesion, the UspF and UspG proteins exhibit the exact opposite effects. We suggest that the Usp proteins have evolved different physiological functions that reprogram the cell towards defense and escape during cellular stress.

Bacterial Adhesion↗

ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1.

ATF6, a member of the leucine zipper protein family, can constitutively induce the promoter of glucose-regulated protein (grp) genes through activation of the endoplasmic reticulum (ER) stress element (ERSE). To understand the mechanism of grp78 induction by ATF6 in cells subjected to ER calcium depletion stress mediated by thapsigargin (Tg) treatment, we discovered that ATF6 itself undergoes Tg stress-induced changes. In nonstressed cells, ATF6, which contains a putative short transmembrane domain, is primarily associated with the perinuclear region. Upon Tg stress, the ATF6 protein level dropped initially but quickly recovered with the additional appearance of a faster-migrating form. This new form of ATF6 was recovered as soluble nuclear protein by biochemical fractionation, correlating with enhanced nuclear localization of ATF6 as revealed by immunofluorescence. Optimal ATF6 stimulation requires at least two copies of the ERSE and the integrity of the tripartite structure of the ERSE. Of primary importance is a functional NF-Y complex and a high-affinity NF-Y binding site that confers selectivity among different ERSEs for ATF6 inducibility. In addition, we showed that YY1 interacts with ATF6 and in Tg-treated cells can enhance ATF6 activity. The ERSE stimulatory activity of ATF6 exhibits properties distinct from those of human Ire1p, an upstream regulator of the mammalian unfolded protein response. The requirement for a high-affinity NF-Y site for ATF6 but not human Ire1p activity suggests that they stimulate the ERSE through diverse pathways.

3T3 Cells↗

Mitochondrial respiratory electron carriers are involved in oxidative stress during heat stress in Saccharomyces cerevisiae.

In the present study we sought to determine the source of heat-induced oxidative stress. We investigated the involvement of mitochondrial respiratory electron transport in post-diauxic-phase cells under conditions of lethal heat shock. Petite cells were thermosensitive, had increased nuclear mutation frequencies, and experienced elevated levels of oxidation of an intracellular probe following exposure to a temperature of 50 degrees C. Cells with a deletion in COQ7 leading to a deficiency in coenzyme Q had a much more severe thermosensitivity phenotype for these oxidative endpoints following heat stress compared to that of petite cells. In contrast, deletion of the external NADH dehydrogenases NDE1 and NDE2, which feed electrons from NADH into the electron transport chain, abrogated the levels of heat-induced intracellular fluorescence and nuclear mutation frequency. Mitochondria isolated from COQ7-deficient cells secreted more than 30 times as much H(2)O(2) at 42 as at 30 degrees C, while mitochondria isolated from cells simultaneously deficient in NDE1 and NDE2 secreted no H(2)O(2). We conclude that heat stress causes nuclear mutations via oxidative stress originating from the respiratory electron transport chains of mitochondria.

Cell Nucleus↗