Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of the heme oxygenase-1 (HO-1) protein, also called HSP32, was compared to HSP70 heat shock protein induction following focal ischemia. Adult Sprague-Dawley male rats (n = 14) were subjected to either 30 min or 2 h of focal cerebral ischemia using the suture, middle-cerebral-artery (MCA) occlusion model. Controls (n = 4) had sham surgery. Following 24 h of reperfusion, subjects were killed and their brains stained immunocytochemically for HO-1 and the HSP70 heat shock proteins. One day following 30 min of ischemia, HO-1 and HSP70 staining in striatum occurred mainly in endothelial cells in infarcts and in glial cells surrounding the areas of infarction. Following the 30 min ischemia HO-1 was not induced in cortex whereas HSP70 was induced in cortical neurons in the MCA distribution. One day following 2 h of MCA ischemia, both HO-1 and HSP70 were induced in neurons in cortex in the MCA distribution. HO-1, however, was induced in glial cells throughout ipsilateral cortex, inside as well as outside the MCA distribution. This suggests that translation and/or transcription of the HO-1 and HSP70 genes are blocked in neurons and glia destined to die within infarcts, whereas translation of these stress genes continues in the endothelial cells. The duration of ischemia required to induce HSP70 in cortical neurons appears to be less than that required to induce HO-1 in cortical glia. Prolonged spreading depression and/or diffuse hemispheric ischemia may induce HO-1 in glia throughout the ipsilateral cortex via immediate early gene activation of the AP-1 site in the HO-1 promoter. Since HO-1 degrades heme, a pro-oxidant, to antioxidant molecules, the induction of HO-1 may augment oxidative defense mechanisms compromised by cerebral ischemia.
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PMID:Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. 873 52

Stress proteins, including the 70 kD heat shock protein (HSP70), are induced in injured cells. The present study was designed to characterize the cells injured by global ischemia in rat brain. Adult rats were subjected to forebrain ischemia using bilateral carotid occlusion and systemic hypotension. HSP70 protein immunostaining of brain sections was performed using the C92 monoclonal antibody one day later. HSP70 immunoreactive cells were found in many brain regions including cortex. HSP70 positive neurons in cortex were found in certain laminae, especially layers 2 and 3. Acid fuchsin positive neurons, cells presumed to be dead, were located only in the layers of cortex where HSP70 immunoreactive neurons were found and were infrequent compared to the large number of HSP70 positive neurons. HSP70 immunoreactive glial cells were detected at the margins of ischemic areas, and were mostly OX42 immunoreactive microglia plus some GFAP immunoreactive astrocytes. In some animals HSP70 stained bipolar cells were detected in the striatum and in white matter which may be type 2 astrocytes. These findings confirm that global ischemia injures microglia and astrocytes, and that cells in a given ischemic region sustain varying degrees of injury--from the HSP70 stained neurons that likely survive the ischemia to acid fuchsin stained cells that die.
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PMID:HSP70 heat shock protein induction following global ischemia in the rat. 875 Aug 37

It has been reported that ischemic preconditioning of the heart or brain has a possible relevance to heat shock protein (HSP). It is still unknown, however, whether HSP induced by means of ischemic preconditioning of the liver is a direct factor in the acquisition of tolerance to succeeding ischemia-reperfusion injury. In the present study we used ischemic preconditioning of the liver to verify the effects of induced HSP72 in the liver on the subsequent longer warm ischemia and reperfusion. Rats preconditioned with short-term (15-minute) ischemia were compared with rats preconditioned by heat exposure or with control rats. After a 48-hour recovery from the sublethal stress for preconditioning, all rats were exposed to longer (30-minute) warm ischemia and reperfusion. Forty-eight hours after ischemic preconditioning, HSP72 was clearly induced in the liver, as well as in the liver preconditioned with heat shock, but not in the kidney or heart. This ischemic preconditioning also attenuated the liver damage in the subsequent ischemia-reperfusion injury, improving the restoration of hepatic function during reperfusion and resulting in higher postischemic rat survival. According to the proposed model of tolerance acquisition for ischemia-reperfusion injury by stress preconditioning, these observations support the speculation that the induced HSP72 plays some beneficial role in this protection mechanism.
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PMID:Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury. 878 32

The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.
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PMID:Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein. 881 12

Intra-ischemic hypothermia has been demonstrated to be protective against ischemic neuronal injury. The present study examined the effect of moderate hypothermia on the expression of heat shock protein (HSP)-72 following transient forebrain ischemia in gerbils by immunohistochemistry. Global forebrain ischemia with concurrent moderate hypothermia (30 degrees C) was induced in gerbils by 10-minute bilateral carotid artery occlusion followed by recirculation periods of 1 hour (h), 6h, 24h, and 48h. Normothermic forebrain ischemic animals with similar recirculation periods were utilized for comparison of the HSP expression. Sham-operated normothermic and hypothermic animals were also included. 72-kDa heat shock protein immunoreactivity was demonstrated in the hippocampus and neocortex of the normothermic ischemic animals following 24h and 48h recirculation similar to that reported previously. However, the immunoreactivity was absent in the brains of the animals subjected to hypothermic ischemia or sham-operation. Only the ependymal cells were immunopositive in all hypothermic brains as was the case with all normothermic brains. The hypothermic ischemic brains showed no significant necrosis in the hippocampus. These findings suggest that the protection of ischemic neuronal necrosis conferred by intra-ischemic hypothermia is not associated with induction of HSP-72 protein and that mechanisms other then HSP-72 protein induction are likely to be responsible for this neuroprotective effect.
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PMID:The effect of hypothermia on induction of heat shock protein (HSP)-72 in ischemic brain. 884 92

Sublethal heat shock has been shown to produce tolerance in cells and tissues subsequently exposed to heat or ischemia/ATP depletion. We tested whether heating LLC-PK1 cells for 2 h at 42 degrees C induced heat shock protein-70 (HSP-70) gene expression and conferred tolerance against subsequent cyclosporine A (CyA) toxicity. HSP-70 mRNA was increased immediately after heat shock, returning to baseline by 4 h. HSP-70 protein increased by 1 h after heat shock and declined thereafter, approaching baseline after 72 h. Cells heat shocked at 4 and 24 h prior to CyA exposure were significantly more viable than controls, at CyA concentrations near the median lethal dose (LD50). Cytoprotection declined with time after heat shock, concurrent with declining HSP-70 protein levels. Sublethal CyA exposure (50 micrograms/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 micrograms/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 micrograms/ml) produced significant cytoprotection compared with untreated controls. In conclusion, HSP-70 protein induction by sublethal heat shock or CyA exposure was associated with tolerance against subsequent lethal CyA exposure.
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PMID:Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity. 885 18

Stress proteins are induced after a variety of neuronal injuries. The inducible 72-kDa heat shock protein (hsp70) is a stress protein that protects neurons from glutamate toxicity in vitro. Hsp70 has also been proposed to underlie the phenomenon of ischemic tolerance whereby brief sublethal intervals of global ischemia protect the hippocampus from subsequent lethal prolonged ischemia. To determine if the phenomenon of tolerance occurs in cortex after focal ischemia, the rat middle cerebral artery (MCA) was occluded by the suture method. Three 10-min intervals of transient ischemia (3 x 10-isc) separated by 45-min periods of reperfusion made up the most effective paradigm of preconditioning ischemia studied, and substantially reduced the volume of infarction 72 h after subsequent 100-min MCA occlusion. This approach induced protection if the interval between the 3 x 10-isc and the 100-min ischemia was 2, 3, or 5 days but not 1 or 7 days. Three 10-min intervals of transient ischemia alone produced minimal histological changes in the cortex at 72 h. Moreover, there were no significant changes in regional cerebral blood flow in the tolerant regions at 72 h after 3 x 10-isc before or during MCA occlusion. To explore the role of stress proteins in the induction of tolerance, expression of hsp70 and the glucose-regulated proteins grp75 and grp78 were studied. Samples from tolerant regions of the brain that had undergone preconditioning ischemia were evaluated at 1, 2, 3, 5, 7, and 14 days after 3 x 10-isc by Western blot analysis. The time course of hsp70 expression most closely correlated with tolerance. Hsp70 protein expression increased during times when tolerance was present (at 2-5 days) but did not increase thereafter (at 7 and 14 days). However, hsp70 was also increased before tolerance was present (at 1 day). Immunocytochemistry showed that hsp70 protein was expressed in neurons in the tolerant regions 24 h after 3 x 10-isc and was expressed in both neurons and glia after 72 h. Although immunocytochemistry suggested that there was increased neuronal expression of grp75 and grp78, no significant differences were found in protein expression as determined by Western blot before (at 1 day), during (at 2-5 days), and after (at 7 days and thereafter) tolerance. Thus, the time course of grp75 and grp78 expression did not correlate with that of tolerance. This model of ischemic tolerance is a useful method by which mechanisms of endogenous neuroprotection may be explored.
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PMID:Stress proteins and tolerance to focal cerebral ischemia. 896 95

Recently, preinduction of the heat shock response has been shown to protect CNS neurons undergoing various stressful insults, e.g., heat, ischemia, or exposure to excitotoxins. However, it is not known which of the proteins induced by the heat shock response mediate the protective effects. Previous correlative evidence points to a role for the highly stress-induced 72-kDa heat shock protein (hsp72). However, it is not known whether hsp72 expression alone can protect against a range of acute neuronal insults. We constructed a herpes simplex virus-1 vector carrying the rat brain stress-inducible hsp72 gene and the Escherichia coli lacZ (marker) gene. Infection with the vector caused hippocampal neurons to coexpress hsp72 and beta-galactosidase. Infection with a control vector led to marker gene expression only. Overexpression of hsp72 protected cultured hippocampal neurons against a heat shock but not against the metabolic toxin 3-nitropropionic acid or the excitotoxin glutamate. This is the first published report of protection following heat shock protein transfection in CNS neurons.
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PMID:Defective herpes simplex virus vectors expressing the rat brain stress-inducible heat shock protein 72 protect cultured neurons from severe heat shock. 904 41

The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.
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PMID:Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model. 912 12

The cerebral stress response is examined following a variety of pathological conditions such as focal and global ischemia, administration of excitotoxins, and hyperthermia. Expression of 72 kDa heat shock protein (Hsp70) and hsp70 mRNA, the mechanism underlying induction of hsp70 mRNA involving activation of heat shock factor 1, and inhibition of cerebral protein synthesis are different aspects of the stress response considered here. The results are compared with those in the literature on induction, transcriptional regulation, expression, and cellular location of Hsp70, with a view to getting more insight into the function of the stress response in the injured brain. The present results illustrate that Hsp70 can be expressed in cells affected at various degrees following an insult that will either survive or dic as the brain lesion develops, depending on the severity of cell injury. This indicates that, under certain circumstances, synthesized Hsp70 might be necessary but not sufficient to ensure cell survival. Other situations involve uncoupling between synthesis of hsp70 mRNA and protein, probably due to very strict protein synthesis blockade, and often result in cell loss. Cells eventually will die if protein synthesis rates do not go back to normal after a period of protein synthesis inhibition. The stress response is a dynamic event that is switched on in neural cells sensitive to a brain insult. The stress response is, however, tricky, as affected cells seem to need it, have to deal transiently with it, but eventually be able to get rid of it, in order to survive. Putative therapeutic treatments can act either selectively, potentiating the synthesis of Hsp70 protein and recovery of protein synthesis, or preventing the stress response by deadening the insult severity.
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PMID:The heat shock stress response after brain lesions: induction of 72 kDa heat shock protein (cell types involved, axonal transport, transcriptional regulation) and protein synthesis inhibition. 917 59


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