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Decline of shear stress-induced activation of extracellular signal-regulated kinases, but not stress-activated protein kinases, in in vitro propagated endothelial cells.

We investigated the involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways in human endothelial cells in response to shear stress and alterations of these kinases in in vitro-propagated endothelial cells (ECs). Potent activation (10-fold) of extracellular signal-regulated kinase (ERK2), a member of the MAPK family, occurred within 10 min of shear stress (5 dynes/cm2), whereupon rapid inactivation ensued. Shear stress also induced activation of stress-activated protein kinase (SAPK) or c-Jun NH2-terminal protein kinase (JNK) in ECs. Suramin pretreatment completely inhibited shear stress stimulation of ERK2, but not SAPK/JNK, highlighting a role for growth factor receptors in ERK activation. Translocation of ERK2 from the cytoplasm to the nucleus was observed in shear-stressed endothelial cells. In addition, we compared activities of MAPKs in shear-stressed cells derived from passages 4 and 10 (older). The magnitude of ERK2 activation was significantly lower in aged ECs compared to those of passage 4, while SAPK/JNK was not altered in the in vitro aged ECs. A similar level of ERK2 activation was found in both young and older cells stimulated with phorbol-12-myristate-13-acetate (PMA), indicating an age-related alteration of the plasma membrane. Taken together, these findings suggest that MAP kinase activation may be crucial for the expression of many genes in ECs stimulated by shear stress, and that an alteration in MAPK activities could contribute to the age-related decline in proliferative capacity.

Calcium-Calmodulin-Dependent Protein Kinases↗

Potential role of mechanical stress in the etiology of pediatric heart disease: septal shear stress in subaortic stenosis.

OBJECTIVES: The objective of this study was to show elevations in septal shear stress in response to morphologic abnormalities that have been associated with discrete subaortic stenosis (SAS) in children. Combined with the published data, this critical connection supports a four-stage etiology of SAS that is advanced in this report. BACKGROUND: Subaortic stenosis constitutes up to 20% of left ventricular outflow obstruction in children and frequently requires surgical removal, and the lesions may reappear unpredictably after the operation. The etiology of SAS is unknown. This study proposes a four-stage etiology for SAS that I) combines morphologic abnormalities, II) elevation of septal shear stress, III) genetic predisposition and IV) cellular proliferation in response to shear stress. METHODS: Morphologic structures of a left ventricular outflow tract were modeled based on measurements in patients with and without SAS. Septal shear stress was studied in response to changes in aortoseptal angle (AoSA) (120 degrees to 150 degrees), outflow tract convergence angle (45 degrees, 22.5 degrees and 0 degree), presence/location of a ventricular septal defect (VSD) (3-mm VSD; 2 and 6 mm from annulus) and shunt velocity (3 and 5 m/s). RESULTS: Variations in AoSA produced marked elevations in septal shear stress (from 103 dynes/cm2 for 150 degrees angle to 150 dynes/cm2 for 120 degrees angle for baseline conditions). This effect was not dependent on the convergence angle in the outflow tract (150 to 132 dynes/cm2 over full range of angles including extreme case of 0 degree). A VSD enhanced this effect (150 to 220 dynes/cm2 at steep angle of 120 degrees and 3 m/s shunt velocity), consistent with the high incidence of VSDs in patients with SAS. The position of the VSD was also important, with a reduction of the distance between the VSD and the aortic annulus causing further increases in septal shear stress (220 and 266 dynes/cm2 for distances of 6 and 2 mm from the annulus, respectively). CONCLUSIONS: Small changes in AoSA produce important changes in septal shear stress. The levels of stress increase are consistent with cellular flow studies showing stimulation of growth factors and cellular proliferation. Steepened AoSA may be a risk factor for the development of SAS. Evidence exists for all four stages of the proposed etiology of SAS.

Adolescent↗

Behavioural changes after different stress paradigms: prepulse inhibition increased after physical, but not emotional stress.

Physical (PS) and emotional (ES) stress have opposite long-term effects on open field behaviour, i.e., response to novelty. PS induced a long-term reduction in locomotor activity, while ES increased it. Additionally, sensitivity to rewarding stimuli was differentially affected by PS and ES. Whether the stress effects were specific for locomotor activity and reward or if these two stress treatments also have differential effects on other behaviours and brain functions is not known. In the present study, temperature regulation, sensory gating, learning capacity, locomotor activity and coping style were examined. PS consisted of a repeated mild foot shock treatment, which the ES animals witnessed. The tests pose additional challenges, to which all groups can respond differently depending on their previous experience. All tests were performed several days after the last stress treatment. Stress effects were specifically observed on locomotor activity, startle response and prepulse inhibition (PPI). The PS animals showed a potentiated inhibition of the startle when a prepulse (PPI) was used, although the initial startle response was already significantly lower than that of controls. ES animals did not differ from controls on PPI and startle. Additionally PS animals showed an initial decrease in activity, which turned into an increase when the tests continued. ES showed a constant increase in activity compared to controls. Stress effects on the tests for other brain processes and behaviour were not found. In addition, PS animals appeared to be less sensitive to the dopamine agonist apomorphine than control animal. In summary, physical and emotional stress induce differential changes on locomotor activity, startle response and PPI. Underlying mechanisms explaining the differences in stress effects are discussed, i.e., the role of the mesolimbic dopamine system and opioid systems.

Animals↗

Cell loading with laser-generated stress waves: the role of the stress gradient.

PURPOSE: To determine the dependence of the permeabilzation of the plasma membrane on the characteristics of laser-generated stress waves. METHODS: Laser pulses can generate stress waves by ablation. Depending on the laser wavelength, fluence, and target material, stress waves of different characteristics (rise time, peak stress) can be generated. Human red blood cells were subjected to stress waves and the permeability changes were measured by uptake of extracellular dye molecules. RESULTS: A fast rise time (high stress gradient) of the stress wave was required for the permeabilization of the plasma membrane. While the membrane was permeable, the cells could rapidly uptake molecules from the surrounding medium by diffusion. CONCLUSIONS: Stress waves provide a potentially powerful tool for drug delivery.

Cell Membrane Permeability↗

Inherited stress resistance and longevity: a stress theory of ageing.

Ageing is considered in the context of the abiotic stresses to which free-living organisms are normally exposed. Assuming that the primary target of selection of stress is at the level of energy carriers, trade-offs under the rate-of-living theory of ageing predict increased longevity from selection for stress resistance. Changes in longevity then become incidental to selection for stress resistance. I therefore suggest the reformulation of the rate-of-living theory to become a stress theory of ageing. This directly incorporates the characteristics of habitats in nature. Under this theory, the primary trait inherited is resistance to stress. Consequently, at extreme ages those with inherited resistance to abiotic stress should dominate. Furthermore, the reduction in homeostasis manifested by deteriorating ability to adapt to abiotic stress as ageing proceeds, should be slowest in those surviving longest.

Aging↗

Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth.

Saccharomyces cerevisiae neutral trehalase, encoded by NTH1, controls trehalose hydrolysis in response to multiple stress conditions, including nutrient limitation. The presence of three stress responsive elements (STREs, CCCCT) in the NTH1 promoter suggested that the transcriptional activator proteins Msn2 and Msn4, as well as the cAMP-dependent protein kinase (PKA), control the stress-induced expression of Nth1. Here, we give direct evidence that Msn2/Msn4 and the STREs control the heat-, osmotic stress- and diauxic shift-dependent induction of Nth1. Disruption of MSN2 and MSN4 abolishes or significantly reduces the heat- and NaCl-induced increases in Nth1 activity and transcription. Stress-induced increases in activity of a lacZ reporter gene put under control of the NTH1 promoter is nearly absent in the double mutant. In all instances, basal expression is also reduced by about 50%. The trehalose concentration in the msn2 msn4 double mutant increases less during heat stress and drops more slowly during recovery than in wild-type cells. This shows that Msn2/Msn4-controlled expression of enzymes of trehalose synthesis and hydrolysis help to maintain trehalose concentration during stress. However, the Msn2/Msn4-independent mechanism exists for heat control of trehalose metabolism. Site-directed mutagenesis of the three STREs (CCCCT changed to CATCT) in NTH1 promoter fused to a reporter gene indicates that the relative proximity of STREs to each other is important for the function of NTH1. Elimination of the three STREs abolishes the stress-induced responses and reduces basal expression by 30%. Contrary to most STRE-regulated genes, the PKA effect on the induction of NTH1 by heat and sodium chloride is variable. During diauxic growth, NTH1 promoter-controlled reporter activity strongly increases, as opposed to the previously observed decrease in Nth1 activity, suggesting a tight but opposite control of the enzyme at the transcriptional and post-translational levels. Apparently, inactive trehalase is accumulated concomitant with the accumulation of trehalose. These results might help to elucidate the general connection between control by STREs, Msn2/Msn4 and PKA and, in particular, how these components play a role in control of trehalose metabolism.

Base Sequence↗

Resistance of extrathymic T cells to stress and the role of endogenous glucocorticoids in stress associated immunosuppression.

When mice were exposed to restraint stress for 12 or 24 h, severe lymphopenia was induced in all immune system organs, including the liver and the thymus. However, in adrenalectomized mice, this response was completely absent. Phenotypic characterization revealed that interleukin (IL)-2Rbeta+CD3int cells (i.e. extrathymic T cells) with CD4+ phenotype and the NK1.1+ subset of CD3int cells (i.e. NKT cells) in the liver as well as the mature conventional T cells in the thymus were resistant to such stress. In adrenalectomized mice, there was no significant change in the distribution of lymphocyte subsets in all tested organs before stress. Interestingly, the number of lymphocytes in the liver and spleen and the proportion of NKT cells in the liver rather increased after stress in these adrenalectomized mice. Therefore, endogenous steroid hormones were indicated to be important in the induction of immunosuppressive states after stress. Among stress associated cytokines, the secretion of tumour necrosis factor (TNF)-alpha was completely suppressed while that of IL-6 was partially suppressed in adrenalectomized mice. These results suggest that endogenous steroid hormones are important for the induction of the stress associated immunosuppression and that NKT cells are resistant to stress, namely, resistant to exposure to endogenous steroid hormones.

Adrenalectomy↗

Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites: implications for stress-related cortical pathology?

Stress has been shown to affect brain structural plasticity, promote long-term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress-related neural alterations are still poorly understood. Mitogen-activated protein kinase (MAPK) cascades play a crucial role in the transduction of neurotrophic signal from the cell surface to the nucleus and are implicated in the modulation of synaptic plasticity and neuronal survival. An intriguing possibility is that stress might influence brain plasticity through its effects on selective members of such intracellular signalling cascades responsible for the transduction of neurotrophin signals. Here, we have investigated the effects of stress on the expression of three members of the MAPK/extracellular-regulated kinase (ERK) pathway such as phospho-ERK1, phospho-ERK2 and phospho-cAMP/calcium-responsive element-binding protein (CREB) in the adult rat brain. Male rats were subjected to mild footshocks and the patterns of protein expression were analysed after 21 consecutive days of stress. We found that chronic stress induced a pronounced and persistent ERK1/2 hyperphosphorylation in dendrites of the higher prefrontocortical layers (II and III) and a reduction of phospho-CREB expression in several cortical and subcortical regions. We hypothesized that defects in ERK signalling regulation combined with a reduced phospho-CREB activity may be a crucial mechanism by which sustained stress may induce atrophy of selective subpopulations of vulnerable cortical neurons and/or distal dendrites. Thus, ERK-mediated cortical abnormalities may represent a specific path by which chronic stress affects the functioning of cortical structures and causes selective neural network defects.

Animals↗

Work stress and posttraumatic stress disorder in ED nurses/personnel.

INTRODUCTION: Work-related stress in the emergency department previously has been linked to depression and burnout; however, these findings have not been extended to the development of anxiety disorders, such as posttraumatic stress disorder (PTSD). Three sets of factors have been shown to contribute to stress in ED personnel: organizational characteristics, patient care, and the interpersonal environment. The current study addressed whether an association exists between sources of workplace stress and PTSD symptoms. METHOD: Respondents were 51 ED personnel from a hospital in a large Canadian urban center. The majority of respondents were emergency nurses. Respondents completed questionnaires measuring PTSD and sources of work stress and answered a series of questions regarding work-related responses to stress or trauma. RESULTS: Interpersonal conflict was significantly associated with PTSD symptoms. The majority of respondents (67%) believed they had received inadequate support from hospital administrators following the traumatic incident and 20% considered changing jobs as a result of the trauma. Only 18% attended critical incident stress debriefing and none sought outside help for their distress. DISCUSSION: These findings underscore the need for hospital administrations to be aware of the extent of workplace stress and PTSD symptoms in their employees. Improving the interpersonal climate in the workplace may be useful in ameliorating PTSD symptoms.

Adult↗

Sex differences in tail-flick latency of non-stressed and stressed rats.

The present study was conducted to assess whether there are sex differences between male and female subjects in their response to noxious stimuli under non-stressed and stressed conditions. Tail-flick latency assay was used as an experimental tool on 12 adult male and 12 adult female Sprague-Dawley rats before immobilization (i.e., non-stressed condition) and after 30, 120, 240, and 360 min of continuous immobilization (i.e., stressed conditions). It was found that the non-stressed female rats exhibited significantly longer response latency to noxious thermal stimuli than the non-stressed male rats. Stressed conditions caused by immobilization of the animal inside a ventilated restrainer significantly prolonged the tail-flick latency thresholds of both sexes. Female and male rats did not develop any adaptation after 120, 240, and 360 min of immobilization compared to their 30 min of immobilization, as demonstrated by the tail-flick assay. Moreover, the difference in the tail-flick latency between male and female rats was reduced as the duration of immobilization in the restrainer lengthened. At 30 min of immobilization, the significant difference between the sexes reduced to p < .05 compared to p < .01 before immobilization, and to statistically non-significant differences after 120, 240, and 360 min of immobilization. Results from this study suggested that female rats had longer tail-flick latency than male rats in non-stressed environment, and the difference in tail-flick latency after immobilization between the sexes became less significant with time. In addition, 360 min of immobilization was not enough to adapt to the restrainer, as shown by the tail-flick assay.

Animals↗

Standing interface stresses as a predictor of walking interface stresses in the trans-tibial prosthesis.

Interface pressures and shear stresses within the socket, in standing and walking, were measured for two unilateral, male, trans-tibial amputee subjects, during two sessions each. The ratios of equal weight-bearing standing stresses to peak walking stresses showed regional variation, ranging from 0.24:1 for pressure over the anterior region to 1.01:1 for resultant interface shear stress over the lateral region. Interface stresses in standing were only moderate predictors of peak walking stresses. The best correlation coefficient between standing in full weight-bearing and peak walking stress was 0.88 for pressure over the lateral region. As the amputees progressed from minimal to full weight-bearing in standing, and then to walking, the interface stresses increased in a nonlinear fashion, consistent with the assumption that the anterior tibia provides much resistance to the bending moment in the sagittal plane during walking.

Adult↗

Comparison of stress and stress management strategies between lesbian and heterosexual women.

Stress is said to be part of life, but stress may be uniquely experienced by different groups of women. We conducted this study to compare the experiences of stress and the methods of stress management used by lesbian and heterosexual women. A convenience sample of 215 (136 lesbian and 79 heterosexual) urban women was used. All women reported generally good mental health; however, more than 80% of the women reported moderate or severe stress. There were more similarities than differences between the groups, but lesbians reported more stress due to sexual identity, being female, and mental problems, and heterosexual women reported more stress due to parents and children. Both groups used a wide range of stress management strategies, although lesbians more frequently used meditation and therapy.

Adult↗

Moderate psychosocial stress appears not to impair recall of words learned 4 weeks prior to stress exposure.

Recent studies in humans have reported that recall of previously learned material is especially sensitive to the disruptive effects of pharmacologically induced cortisol elevations. Whether similar effects occur after exposure to psychosocial stress remains to be shown. Moreover it is unknown whether stress before or after the initial learning interacts with the later effects of repeated stress on delayed recall (e.g. state-dependent learning). Forty subjects participated in the present experiment. They learned a word list either one hour before or 10 min after exposure to a psychosocial laboratory stressor. Delayed recall was tested 4 weeks later, again either before or after stress. Salivary cortisol levels increased significantly in response to both stress exposures. Stress had no effects on the initial learning and also did not impair delayed recall. Moreover there was no evidence for state-dependent learning. The current data seem to be in conflict with previous studies demonstrating that delayed recall is especially sensitive to elevated cortisol levels. Several reasons for these discrepancies are discussed. Among them is the small sample size, the moderate cortisol increase in response to the second stress exposure but also the long recall delay, which might lead to memory traces less susceptible to stress.

Adult↗

Acute stress impairs recognition for positive words--association with stress-induced cortisol secretion.

Some studies suggest that stress-induced effects of cortisol on memory are modulated by the valence of the stimuli to be learned and retrieved. The present study investigated the effect of acute stress-induced cortisol secretion on acquisition and retrieval of pleasant, unpleasant and neutral words. Sixty healthy men were randomly assigned to one of the three experimental groups. Participants were either exposed to a standardized laboratory stressor (the Trier Social Stress Test) before learning a wordlist, or before retrieval, or were not stressed. Free recall and recognition were tested 24 h later. Free recall was not affected by stress exposure. For recognition, there was no main effect of the stressor, but a main effect of valence and a valence by group interaction emerged: recognition for positive words was significantly impaired when subjects were stressed before retrieval. In addition, a positive correlation between the cortisol response and errors of commission was found. The results suggest that acute stress impairs memory for positive stimuli and that stress-induced cortisol secretion interferes with accuracy of memory retrieval, i.e. the ability to discriminate true memories from false ones.

Acute Disease↗

A pilot study to examine the effects of a mindfulness-based stress-reduction and relaxation program on levels of stress hormones, physical functioning, and submaximal exercise responses.

OBJECTIVE: Stress has been cited as a causal factor in heart disease. The objective of this study was to examine the effects of an 8-week mindfulness-based stress-reduction program on the resting levels of stress hormones, physical functioning, and submaximal exercise responses in women with heart disease. SUBJECTS: Random selection with the numbers 1 and 2 were used to assign 18 women (60 +/-6.3 years old) with documented histories of heart disease to a treatment group (n = 9) or a control group (n = 9). Speilberger's state anxiety scores for the treatment (M = 37.88; standard deviation (SD) = 10.91) and control group (M = 43.22; SD = 12.26) were not significantly different prior to the start of the study. However, their scores fell in the upper percentile rank for normal adults in their age category. INTERVENTION: The intervention was provided one night each week for 2 hours over a period of 8 weeks. The intervention included didactic, inductive, and experiential modes of learning regarding stress responses and mindfulness skill-development training. DESIGN: Pre-post test hormonal measurements and physical function were analyzed using a 2 (group) by 2 (time) analysis of variance (ANOVA) with repeated measures following the 8-week program. Submaximal exercise responses were also compared between the treatment group and the control group following the 8-week program. A 2 (group) by 3 (time) ANOVA with repeated measures was used to analyze the data. SETTINGS/LOCATION: Weekly meetings were held on a university medical school campus. Submaximal exercise responses were recorded while participants cycled on a stationary bike in an applied physiology laboratory following the 8-week program. RESULTS: There were no significant main effects or interaction for the resting levels of stress hormones or physical functioning. There were no significant interactions for the submaximal exercise responses, however, there were significant main effects between groups for ventilation [F(2,32) = 7.65, p < .01, f = 0.8], and between group [F(1,16) = 8.84, p < .01, f = 0.8] and time [F(2,32) = 10.42, p < .01, f = 0.9], for breathing frequency. CONCLUSION: While the 8-week stress reduction program for women with heart disease did not show significant interactions between groups for resting levels of stress hormones, physical functioning, or submaximal exercise responses, there was a significant difference in breathing patterns between the 2 groups during exercise following the mindfulness-based stress-reduction program. There was also a trend for change in the intervention group in the resting levels of cortisol and physical function scores that was not seen in the control group. Future studies could use the effect size generated from this pilot study to calculate the number of subjects needed for adequate power to detect significant differences between groups.

Aged↗

Stress-induced gene expression in Candida albicans: absence of a general stress response.

We used transcriptional profiling to investigate the response of the fungal pathogen Candida albicans to temperature and osmotic and oxidative stresses under conditions that permitted >60% survival of the challenged cells. Each stress generated the transient induction of a specific set of genes including classic markers observed in the stress responses of other organisms. We noted that the classical hallmarks of the general stress response observed in Saccharomyces cerevisiae are absent from C. albicans; no C. albicans genes were significantly induced in a common response to the three stresses. This observation is supported by our inability to detect stress cross-protection in C. albicans. Similarly, in C. albicans there is essentially no induction of carbohydrate reserves like glycogen and trehalose in response to a mild stress, unlike the situation in S. cerevisiae. Thus C. albicans lacks the strong general stress response exhibited by S. cerevisiae.

Candida albicans↗

Isolation and transcription profiling of low-O2 stress-associated cDNA clones from the flooding-stress-tolerant FR13A rice genotype.

BACKGROUND: and Aims Flooding stress leads to a significant reduction in transcription and translation of genes involved in basal metabolism of plants. However, specific genes are noted to be up-regulated in this response. With the aim of isolating genes that might be specifically involved in flooding stress-tolerance mechanism(s), two subtractive cDNA libraries for the flooding-stress-tolerant rice genotype FR13A have been constructed, namely the single and double subtraction libraries (SSL and DSL, respectively). METHODS: To construct the SSL, mRNAs present in the unstressed control FR13A roots were subtracted from the mRNA pool present in low O2-stressed roots of FR13A rice seedlings. The DSL was constructed from mRNAs isolated from the roots of low O2-stressed FR13A rice seedlings from which pools of low-O2-stress up-regulated mRNAs from Pusa Basmati 1 and constitutively expressed mRNAs from FR13A roots were subtracted. RESULTS: In all, 400 and 606 cDNA clones were obtained from the SSL and DSL, respectively. Global transcript profiling by reverse northern analysis revealed that a large number of clones from these libraries were up-regulated by anaerobic stress. Importantly, selective up-regulated clones showed characteristic cultivar- and tissue-specific expression profiles. Sequencing and annotation of the up-regulated clones revealed that specific signal proteins, hexose transporters, ion channel transporters, RNA-binding proteins and transcription factor proteins possibly play important roles in the response of rice to flooding stress. Also a significant number of novel cDNA clones was noted in these libraries. CONCLUSIONS: It appears that cellular functions such as signalling, sugar and ion transport and transcript stability play an important role in conferring higher flooding tolerance in the FR13A rice type.

DNA, Complementary↗

Study to evaluate the effectiveness of stress management workshops on response to general and occupational measures of stress.

This study was designed to evaluate the effectiveness of stress management training workshops within Zeneca Pharmaceuticals. The study was of cross-sectional design, comparing groups of workshop attendees and non-attendees. In addition, self-rated well-being scores of attendees were compared with results obtained pre-workshop and 2-3 months after the workshop. Employees participating in the study were drawn from the Manufacturing, Research and Development, Sales and Marketing sites of Zeneca Pharmaceuticals located in Cheshire, United Kingdom. Three hundred and ninety persons who had participated in stress management workshops since 1988 were matched for age, gender and department with an equal number of employees who had not attended stress management workshops. Outcome measures included self-rated well-being (as measured by the 30-question General Health Questionnaire), knowledge of company guidance on the management of stress in staff, and an assessment of coping strategies. Subjects who had not attended a stress management workshop were much more likely to have a poor understanding of the principles of management of stress in staff [odds ratio (OR) = 8.3; 95% confidence interval (CI) = 3.3-21.3] and more likely to have poor coping skills (OR = 2.8; CI = 1.3-6.1). However, mean scores for the two measures were similar in attendees and non-attendees. Self-rating of current well-being was strongly associated with the life-events score, but not related to workshop attendance. The study indicates that stress management training workshops reduce the prevalence of employees with a poor understanding of the principles of the management of stress in staff and with poor coping strategies. An improvement in the self-rated well-being observed shortly after the workshop was not sustained.

Adaptation, Psychological↗