Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0848237 (acute stress)
4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral ischemia could be observed as acute metabolic crisis, when oxygen and glucose supply is compromised and synthesis of energy is insufficient. Apart from the excitotoxicity, increased production of reactive oxygen species with consequent lipid peroxidation is also included in neuronal cell damage. Furthermore, these toxic compounds could also be produced during the process of secondary inflammation of ischemic tissue. In the early stage of ischemia, as a systemic response to acute stress, there is an increase in glucose level in cerebrospinal fluid (CSF) and peripheral blood. According to the metabolic crisis and acidosis in ischemic brain tissue we investigated index of lipid peroxidation (ILP) and glucose utilization (IGU) in CSF of 53 patients of both sexes, aged 55-70 years with cerebral infarction. Control group comprised 15 patients with sudden onset of motor deficit subjected to diagnostic lumbar radiculography and suspected on discal genesis. ILP in CSF, as the indicator and sequela of neuronal cell membranes damage, was two fold increased in the acute period of cerebral infarction and maximal values (3.5 times) were noticed 24 hours after the ischemic episode compared to controls. Besides the increase in glucose concentration in peripheral blood and CSF of patients with cerebral infarction, IGU was decreased (37%) with minimal values (32%) 24 hours after the ischemia. These changes indicate that glucose is available but cells are incapable to metabolize it. We concluded that ILP and IGU in CSF of patients with cerebral infarction could be indicators of metabolic dysfunction and neuronal cell damage. Also, these results suggest the significance of polyvalent therapy including antioxidative and antiinflammatory agents in acute phase of cerebral ischemia.
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PMID:Index of lipid peroxidation and glucose utilization in the cerebrospinal fluid in patients with cerebral infarction. 1152 60

The hippocampus is an important structure for declarative, spatial, and contextual memory and is implicated in the perception of chronic pain. The hippocampal formation is vulnerable to damage from seizures, ischemia, and head trauma and is particularly sensitive to the effects of adrenal glucocorticoids secreted during the diurnal rhythm and chronic stress. Adrenal steroids typically have adaptive effects in the short run, but promote pathophysiology when there is either repeated stress or dysregulation of the HPA axis. The damaging actions of glucocorticoids under such conditions have been termed "allostatic load", referring to the cost to the body of adaptation to adverse conditions. Adrenal steroids display both protective and damaging effects in the hippocampus. They biphasically modulate excitability of hippocampal neurons, and high glucocorticoid levels and severe acute stress impair declarative memory in a reversible manner. The hippocampus also displays structural plasticity, involving ongoing neurogenesis of the dentate gyrus, synaptogenesis under control of estrogens in the CA1 region, and dendritic remodeling caused by repeated stress or elevated levels of exogenous glucocorticoids in the CA3 region. In all three forms of structural plasticity, excitatory amino acids participate along with circulating steroid hormones. Glucocorticoids and stressors suppress neurogenesis in the dentate gyrus. They also potentiate the damage produced by ischemia and seizures. Moreover, the aging rat hippocampus displays elevated and prolonged levels of excitatory amino acids released during acute stress. Our working hypothesis is that structural plasticity in response to repeated stress starts out as an adaptive and protective response, but ends up as damage if the imbalance in the regulation of the key mediators is not resolved. It is likely that morphological rearrangements in the hippocampus brought on by various types of allostatic load alter the manner in which the hippocampus participates in memory functions and it is conceivable that these may also have a role in chronic pain perception.
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PMID:Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. 1200 27

The creatine kinase (CK) system is involved in the rapid transport of high-energy phosphates from the mitochondria to the sites of maximal energy requirements such as myofibrils and sarcolemmal ion pumps. Hearts of mice with a combined knockout of cytosolic M-CK and mitochondrial CK (M/Mito-CK(-/-)) show unchanged basal left ventricular (LV) performance but reduced myocardial high-energy phosphate concentrations. Moreover, skeletal muscle from M/Mito-CK(-/-) mice demonstrates altered Ca2+ homeostasis. Our hypothesis was that in CK-deficient hearts, a cardiac phenotype can be unmasked during acute stress conditions and that susceptibility to ischemia-reperfusion injury is increased because of altered Ca2+ homeostasis. We simultaneously studied LV performance and myocardial Ca2+ metabolism in isolated, perfused hearts of M/Mito-CK(-/-) (n = 6) and wild-type (WT, n = 8) mice during baseline, 20 min of no-flow ischemia, and recovery. Whereas LV performance was not different during baseline conditions, LV contracture during ischemia developed significantly earlier (408 +/- 72 vs. 678 +/- 54 s) and to a greater extent (50 +/- 2 vs. 36 +/- 3 mmHg) in M/Mito-CK(-/-) mice. During reperfusion, recovery of diastolic function was impaired (LV end-diastolic pressure: 22 +/- 3 vs. 10 +/- 2 mmHg), whereas recovery of systolic performance was delayed, in M/Mito-CK(-/-) mice. In parallel, Ca2+ transients were similar during baseline conditions; however, M/Mito-CK(-/-) mice showed a greater increase in diastolic Ca2+ concentration ([Ca2+]) during ischemia (237 +/- 54% vs. 167 +/- 25% of basal [Ca2+]) compared with WT mice. In conclusion, CK-deficient hearts show an increased susceptibility of LV performance and Ca2+ homeostasis to ischemic injury, associated with a blunted postischemic recovery. This demonstrates a key function of an intact CK system for maintenance of Ca2+ homeostasis and LV mechanics under metabolic stress conditions.
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PMID:Creatine kinase-deficient hearts exhibit increased susceptibility to ischemia-reperfusion injury and impaired calcium homeostasis. 1510 71

Bilateral common carotid artery occlusion (BCCAO) produces moderate levels of ischemia in the retina of rats, which may simulate the inflow disturbances in severe carotid artery disease. ERG changes following acute BCCAO have been well described, but the effects of chronic BCCAO on the histopathology of the retina remain to be characterized in a reproducible model. Chronic BCCAO was induced in halothane-anaesthetized male Wistar rats and the retina fixed after 3, 6, or 24 hr, 1 week, and 2, 4, or 6 months. Cell counts and measurements of retinal layers were performed in H&E stained paraffin sections. Immunohistochemistry with a panel of fourteen antibodies served to examine the survival of different retinal cell class, astrocytic reactions and the expression of acute stress response proteins. A lectin method was used to label activated microglial cells. Microglial activation, heme oxygenase-1 upregulation and caspase-3 cleavage occurred during the first 24hr in the absence of overt cell death of retinal ganglion cells (RGC). Three waves of neurodegeneration followed. RGCs were affected after 1 week, followed by neurons in the inner nuclear layer at 2 months, and finally photoreceptors at 4 months. Immunomarkers indicated acute damage to horizontal cells and prolonged survival of amacrine cells. In conclusion, chronic BCCAO produced delayed neuronal death in the retina of adult male Wistar rats. The window of moderate changes of at least 1 day may facilitate molecular studies on retinal ganglion cell loss.
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PMID:Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. 1635 64

The mechanisms controlling ATP generation in the transition from normal resting conditions to either high work states or ischemia are poorly understood. ATP generation depends upon compartmentation between the mitochondria and cytosol of metabolic pathways and key energy transfer species that cannot be easily assessed experimentally. We developed a multicompartment mathematical model of cardiac metabolism to simulate the metabolic responses to ischemia and increased workload. The model is based on mass balances, transport, and metabolic processes in cardiac tissue, and has three distinct compartments (blood, cytosol, and mitochondria). In addition to distinguishing between cytosol and mitochondria, the model includes a cytosolic subcompartment for glycolytic metabolic channeling. The model simulations predict the rapid activation of glycogenolysis and lactate production at the onset of ischemia, and support the concept of localization of glycolysis to a cytosolic subcompartment. In addition, simulations show that mitochondrial NADH/NAD(+) is primarily determined by oxygen consumption during ischemia, while cytosolic NADH/NAD(+) and lactate production are largely a function of glycolytic flux during the initial phase, and is controlled by mitochondrial NADH/NAD(+) and the malate-aspartate shuttle during the steady state. Finally, the model predicts that metabolic activation with an abrupt increase in workload requires parallel activation of ATP hydrolysis, glycolysis, mitochondrial dehydrogenases, the electron transport chain, and ADP phosphorylation. Taken together, these studies demonstrate the importance of metabolic compartmentation in the regulation of cardiac energetics in response to acute stress, and they highlight the usefulness of computational models in this line of investigation.
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PMID:Role of cellular compartmentation in the metabolic response to stress: mechanistic insights from computational models. 1713 80

It is known that many tubular proteins are involved in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which causes 8-10% of the cases of end-stage renal disease (ESRD) worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli such as ischemia or toxicity. In the present study, serum and urinary NGAL levels were evaluated in 26 ADPKD subjects. Both levels were significantly higher in patients than in controls (sNGAL 174 +/- 52 vs. 50 +/- 27 ng/ml, p < 0.05; uNGAL 119 +/- 42 vs. 7 +/- 6 ng/ml, p < 0.005) and a close correlation was also found between these parameters and the residual renal function (sNGAL/GFR: r = -0.8, p = 0.006; sNGAL/Creatinine: r = 0.9, p = 0.007; uNGAL/GFR: r = -0.49, p < 0.05; uNGAL/Creatinine: r = 0.84, p < 0.001). Patients were further divided into two groups according to the cystic development assessed with echotomography; subjects with higher cystic growth (HCG) presented higher sNGAL and uNGAL levels with respect to others (sNGAL: 242 +/- 89 vs. 88 +/- 34 ng/ml, p < 0.05; uNGAL: 158 +/- 45 vs. 73 +/- 27 ng/ml, p < 0.05). The strict correlation between NGAL levels and residual renal function is perfectly in accord with recent studies on patients with other ESRD-associated diseases. We can hypothesize that tubular cells produce big quantities of NGAL as a consequence of increased apoptosis following chronic damage or as a compensatory response, similar to that observed in acute stress conditions (ischemia, toxicity ...). Finally, our last finding that patients with HCG showed higher levels of NGAL suggests that this protein could be also involved in the cyst growth process, as previously reported about epithelial and tumoral expansion.
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PMID:Neutrophil gelatinase-associated lipocalin in patients with autosomal-dominant polycystic kidney disease. 1757 Sep 4

CryAB and HSPB2 are small heat shock proteins constitutively expressed in the heart. CryAB protects cytoskeletal organization and intermediate filament assembly; the functions of HSPB2 are unknown. The promoters of CryAB and HSPB2 share regulatory elements, making identifying their separate functions difficult. Here, using a genetic approach, we report distinct roles for these sHSPs, with CryAB protecting mechanical properties and HSPB2 protecting energy reserve. Isolated hearts of wild type mice (WT), mice lacking both sHSPs (DKO), WT mice overexpressing mouse CryAB protein (mCryAB(Tg)), and mice with no HSPB2 made by crossing DKO with mCryAB(Tg) (DKO/mCryAB(Tg)) were stressed with either ischemia/reperfusion or inotropic stimulation. Contractile performance and energetics were measured using 31P NMR spectroscopy. Ischemia/reperfusion caused severe diastolic dysfunction in DKO hearts. Recovery of [ATP] and [PCr] during reperfusion was impaired only in DKO/mCryAB(Tg). During inotropic stimulation, DKO/mCryAB(Tg) showed blunted systolic and diastolic function and revealed massive energy wasting on acute stress: |deltaG(-ATP)| decreased in DKO by 6.4 +/- 0.7 and in DKO/mCryAB(Tg) by 5.5 +/- 0.8 kJ/mol compared with only approximately 3.3 kJ/mol in WT and mCryAB(Tg). Thus, CryAB and HSPB2 proteins play nonredundant roles in the heart, CryAB in structural remodeling and HSPB2 in maintaining energetic balance.
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PMID:Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. 1784 79

ErbB receptor tyrosine kinases are important in maintaining the long-term structural integrity of the heart and in the induction of hypertrophy. In addition, in vivo activation of ErbB1 by epidermal growth factor (EGF) protects the heart against acute stress-induced damage. We examined here whether the ErbB sytem acutely protects the isolated heart in which stress was induced in vitro by ischemia combined with epinephrine infusion (EPI). In perfused mouse hearts, EGF induced Tyr-phosphorylation of ErbB1 but not ErbB2. Neuregulin-1beta (NRG-1beta) induced Tyr-phosphorylation of both ErbB4 and ErbB2. We also found differences in the signaling cascades activated by each growth factor. To stress the perfused mouse heart, we combined EPI with low-flow ischemia. This resulted in (i) loss of left ventricle contraction force ( + dP/dt(max)) and developed pressure (LVDP) after a short period of hypercontractility, (ii) enhanced anaerobic metabolism (lactate production), and (iii) myocyte injury (lactate dehydrogenase (LDH) release). EGF and NRG-1beta had different effects on stressed-heart contractility. EGF reduced to a half the loss of both + dP/dt(max) and LVDP. In contrast, NRG-1beta exacerbated the hypercontractility soon after reperfusion. This is coincident with a transient increase in coronary flow after reperfusion. In spite of these differences in contraction, both EGF and NRG-1beta induced similar early protection as shown by the reduction of LDH release. Our results show that the ErbB system protects the perfused heart against damage induced by acute stress. They reinforce the relevance of ErbB receptors and ligands in cardiac physiology.
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PMID:ErbB receptors protect the perfused heart against injury induced by epinephrine combined with low-flow ischemia. 1937 Apr 75

Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.
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PMID:Tart cherry juice decreases oxidative stress in healthy older men and women. 1969 30

Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2-4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.
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PMID:Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice. 1987 45


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