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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardial ischemia initiates a cascade of cellular events that lead to irreversible injury. We previously described the transient nature of heat-shock induced cardioprotection; treatment with a catalase inhibitor abolished the cytoprotective actions without affecting expression levels of HSP71. Repeated, transient ischemic episodes augment the ischemic tolerance of affected myocardium but the fundamental cytoprotective mechanism(s) for both "early" and "delayed" preconditioning remains unclear. Increased cellular induction of protooncogenes, heat shock genes, and downstream effector proteins might play critical roles in the cytoprotection afforded by delayed preconditioning. We measured c-fos, c-jun, c-myc, and hsp70 induction in preconditioned (2 x 5-min ischemia/10-min reperfusion) and control rabbit hearts that either underwent 30- or 120-min coronary occlusion and 60-min reperfusion, or did not undergo subsequent sustained ischemia; the latter hearts were allowed to recover for 0, 1, 3, 6, 24, 48, 72, or 96 hours. Both c-fos and c-jun in ischemic tissue were strongly induced by ischemia-reperfusion injury and preconditioning pretreatment. However, expression levels diminished significantly by 1-h reperfusion and remained depressed during the 96-h recovery period. Hsp70 (inducible) mRNA expression levels were highest primarily in ischemic myocardium after 6-h recovery post-preconditioning; Hsp70 levels in ischemic myocardium were slightly stronger after 48-h recovery but subsequently diminished to barely detectable levels by 96-h post-preconditioning. Induction of c-fos and c-jun preceded that of Hsp70. These findings support the concept that upregulation of immediate early genes and heat shock genes plays an important role in myocardial adaptation to acute ischemic stress.
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PMID:Cardiac adaptation to ischemia-reperfusion injury. 1041 23

Cerebral ischemia induces immediate early genes such as c-fos and stress genes such as hsp70. In this study, the spatial relationships between c-fos and hsp70 mRNA expression and changes detectable with diffusion and perfusion magnetic resonance (MR) imaging were examined. The middle cerebral artery (MCA) of young adult rats was occluded for 30 or 60 min. Diffusion MR (D-MR) images were acquired continuously during the ischemic period and dysprosium-contrast perfusion (P-MR) images were acquired at the end of the ischemic period. C-fos and hsp70 mRNA expression were examined with in situ hybridization. The most significant finding of this work was that for both durations of ischemia, c-fos induction was observed in cortical and sub-cortical regions exhibiting a transient reduction in the apparent diffusion coefficient of water (ADC). Transients which occurred on a time scale of 3 min may have been caused by spreading depression. Those occurring on a 10-min time scale may have been caused by an initial reduction in blood flow with occlusion that was followed by an ischemia-induced increase in collateral blood flow. P-MR imaging showed that perfusion in c-fos positive regions was higher than in regions with persistently reduced ADC. Hsp70 induction did not correlate with transient ADC reduction. It was induced in the MCA territory in regions showing persistent ADC changes, with induction being greatest at the periphery of these regions. It was also induced in regions that exhibited both spontaneous reversal of the diffusion changes and decreased perfusion.
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PMID:Transient MRI-detected water apparent diffusion coefficient reduction correlates with c-fos mRNA but not hsp70 mRNA induction during focal cerebral ischemia in rats. 1048 94

Thermal pretreatment improves cardiac recovery from subsequent ischemia/reperfusion. Induction of heat shock proteins (hsps) may contribute to this protection. We have demonstrated that augmentation of the constitutive hsp70 (hsc70) in H9c2 heart myoblasts promotes oxidative resistance. We employed a model oxidant to explore potential target(s) of protection by hsc70. Upon exposure to 54 microM of hydrogen peroxide (H(2)O(2)), hsc70-overexpressing cells exhibited a lower lipid peroxidation than the sham-transfected control. Constitutive hsc70 overexpression, however, did not protect against H(2)O(2)-induced depletion of ATP and glutathione (GSH). Lipid protection also occurred in cells preconditioned at 39 degrees C (selectively induces hsc70) during H(2)O(2) exposure. Interestingly, the protection conferred by hsc70 was comparable in magnitude to that provided by alpha-tocopherol, and was followed with a reduced release of lactate dehydrogenase and a unaltered calcium uptake during H(2)O(2) challenge. Collectively, our observations suggest that hsc70 may preserve membrane function via attenuation of lipid peroxidation during oxidative insult.
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PMID:Constitutive hsp70 attenuates hydrogen peroxide-induced membrane lipid peroxidation. 1055 57

The evolution of brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional protein synthesis and the regional tissue content of ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of DNA double-strand breaks visualized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed protein synthesis was distinctly larger than that in which ATP was depleted. With ongoing ischemia time, the ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed protein synthesis. Expression of hsp70 mRNA occurred mainly in the penumbra (defined as the region of suppressed protein synthesis but preserved ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes. DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the infarct core (defined as the region of suppressed ATP) and never were detected in the penumbra. The late appearance of TUNEL after infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding infarct, the final size of which is heralded by the early inhibition of protein synthesis.
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PMID:Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice. 1069 68

Glial cells in the nervous system can produce nitric oxide in response to cytokines. This production is mediated by the inducible isoform of nitric oxide synthase. Radical oxygen species (ROS) and nitric oxide (NO) derivatives have been claimed to play a crucial role in many different processes, both physiological such as neuromodulation, synaptic plasticity, response to glutamate, and pathological such as ischemia and various neurodegenerative disorders. In the present study we investigated the effects of NO synthase (iNOS) induction in astrocyte cultures on the synthesis of heat shock proteins, the activity of respiratory chain complexes and the oxidant/antioxidant balance. Treatment of astrocyte cultures for 18 hr with LPS and INFgamma produced a dose dependent increase of iNOS associated with an increased synthesis of hsp70 stress proteins. This effect was abolished by the NO synthase inhibitor L-NMMA and significantly decreased by addition of SOD/CAT in the medium. Time course experiments showed that iNOS induced protein expression increased significantly by 2 hr after treatment with LPS and INFgamma and reached a plateau at 18 hr; hsp70 protein synthesis peaked around 18 and 36 hr after the same treatment. Addition to astrocytes of the NO donor sodium nitroprusside resulted in a dose dependent increase in hsp70 protein that was comparable to that found after a mild heat shock. Additionally, a decrease in cytochrome oxidase activity, a marked decrease in ATP and protein sulfhydryl contents, an increase in the activity of the antioxidant enzymes mt-SOD and catalase were found which were abolished by L-NMMA. These findings suggest the importance of mitochondrial energy impairment as a critical determinant of the susceptibility of astrocytes to neurotoxic processes and point to a possible pivotal role of hsp70 in the signalling pathways of stress tolerance.
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PMID:Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. 1082 Apr 32

The effects of mild hypothermia on the apparent diffusion coefficient of water (ADC) and expression of c-fos and hsp70 mRNA were examined during acute focal cerebral ischemia. Young adult rats were subjected to 60-min middle cerebral artery occlusion under either normothermia (37.5 degrees C) or hypothermia (33 degrees C). Diffusion-weighted echo-planar magnetic resonance imaging was used to monitor changes in ADC throughout the ischemic period. Perfusion MRI with dysprosium contrast was used at the end of the ischemic period to verify that the occlusion was successful. C-fos and hsp70 mRNA expression were examined with in situ hybridization at the end of the ischemic period. The results indicate that the size of the region that exhibited reduced ADC was smaller during hypothermia than during normothermia. Hypothermia also decreased the frequency of occurrence of transient ADC reductions, especially in dorsal aspects of cortex. Expression of both c-fos and hsp70 mRNA were markedly reduced by hypothermia. Transient ADC reduction and c-fos expression are associated with spreading depression, which is believed to contribute to lesion expansion during acute focal ischemia. The results suggest that part of the neuroprotective effect of hypothermia may be due to a reduced incidence of spreading depression.
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PMID:Mild hypothermia decreases the incidence of transient ADC reduction detected with diffusion MRI and expression of c-fos and hsp70 mRNA during acute focal ischemia in rats. 1113 87

A potential function for inducible heat shock protein 70 (hsp70i) expression in the pathophysiology of ischemic brain has been well documented. The recently cloned hsp70 superfamily member, hsp110, was shown to be highly expressed in the brain and suggested to have a similar functional property as members of the hsp70 family. In this study, as an initial step to probe for its physiological significance in the ischemic brain, cerebral activation and distribution of hsp110 mRNA was comparatively evaluated with that of hsp70i mRNA by in situ hybridization. A rat focal cerebral ischemia model was employed to examine the distribution and localization of hsp110 and hsp70i mRNAs in both affected (ipsilateral) and unaffected (contralateral) hemispheres of the same animal. Our results demonstrated a significant accumulation of hsp110 as well as hsp70i mRNAs following ischemia; although the magnitude and kinetics of induction differ slightly, spatial expression profiles of hsp110 and hsp70i mRNAs were highly correlated in the affected region. In control brain, limited hybridization signal was observed with 3'-untranslated region (UTR) containing hsp110 probe, suggesting a possible existence of inducible hsp110 and a selective recognition of our 3'-UTR containing probe for the inducible hsp110 mRNA species. Subsequent 2D western analysis with Hsp110 specific Ab was consistent with our view, which resolved constitutive and inducible immunostained spots in rat ischemic brain. Considering a regulatory similarity as well as previously documented structural and functional similarities between hsp110 and hsp70i, we propose that coordinated cerebral activation of hsp110 and hsp70i is likely to be of significant relevance in the context of pathophysiology of ischemic brain. Further study is required to characterize the genetic and biochemical nature of rat inducible hsp110 identified in the current study.
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PMID:Cerebral activation and distribution of inducible hsp110 and hsp70 mRNAs following focal ischemia in rat. 1156 77

The cellular localization and spatiotemporal expression pattern of APG-2 protein, a member of the heat shock protein 110 family, were investigated in the rat hippocampus after transient forebrain ischemia. The spatiotemporal patterns of immunoreactivity of both APG-2 and glial fibrillary acidic protein were very similar, indicating that reactive astrocytes express APG-2, which was confirmed by double immunofluorescence histochemistry. Colocalization of APG-2 and a neuronal marker NeuN in the neurons of the CA2 and CA3 subfields was also confirmed.
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PMID:An immunohistochemical study of APG-2 protein in the rat hippocampus after transient forebrain ischemia. 1175 Sep 9

We examined whether heat shock response is affected by experimental hyperlipidemia in rat hearts. Therefore, isolated hearts of male Wistar rats fed a 2% cholesterol-enriched diet or standard diet for 12 weeks were subjected to either 20 min heat stress at 42 degrees C or global normothermic ischemia followed by 120 min normothermic, normoxic perfusion. Both heat stress and ischemia resulted in a significant increase in cardiac mRNA and protein levels of the inducible member of the 70-kDa heat shock protein family (HSP70) when compared to time-matched controls as assessed by reverse transcriptase polymerase chain reaction and Western blotting in hearts of normal rats. However, in hyperlipidemic groups, increase in cardiac hsp70 mRNA and HSP70 protein in response to heat stress and ischemia was markedly attenuated. We further observed that the basal level of hsp70 mRNA was significantly higher in the hyperlipidemic group when compared to normal controls; however, the HSP70 protein level was not different. This is the first demonstration that hyperlipidemia inhibits cardiac heat shock response. We further conclude that basal HSP70 expression might be downregulated at a posttranscriptional level in hyperlipidemia.
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PMID:Hyperlipidemia induced by high cholesterol diet inhibits heat shock response in rat hearts. 1182 Jul 96

Since ADC reduction reflects intracellular edema which is an early indicator of ischemic cellular metabolic stress, we hypothesized that a decrease in ADC as determined by diffusion weighted MR imaging could be attenuated by SOD expression in transgenic mice during reperfusion following focal cerebral ischemia. Diffusion weighted imaging (DWI) was performed to evaluate apparent diffusion coefficient (ADC) reduction by constructing ADC maps with a color scale to localize ADC change in transgenic (Tg) mice expressing human CuZn superoxide dismutase (SOD) and wild type (Wt) mice during 1 h middle cerebral artery occlusion (MCAO) and 1 h reperfusion. Heat shock protein (hsp) 70-kDa mRNA analysis was evaluated as a marker of sublethal cell stress by in situ hybridization after 4 h reperfusion for comparison with Nissl staining of adjacent sections to assess infarction. Sequential ADC maps were prepared in Tg mice with sufficient temporal and spatial resolution to permit comparison with Wt mice. Tg mice showed substantial recovery of the ADC lesion after reperfusion, while Wt mice showed no recovery. There was no difference between Tg and Wt mice in the size or distribution of the ADC lesion during ischemia. The area with strong expression of hsp70 mRNA in the ischemic hemisphere was substantially larger in the Tg mice. Nissl staining showed less damage of brain tissue in Tg mice than Wt mice especially in the cortex after 4 h reperfusion following 1 h MCAO. Results demonstrate that antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h MCAO. Hsp70 could be one of the proteins that mediates protection by SOD against oxidative stress.
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PMID:Transgenic mice expressing human copper-zinc superoxide dismutase exhibit attenuated apparent diffusion coefficient reduction during reperfusion following focal cerebral ischemia. 1214 46


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