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)

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after 2, 5 and 15 min of transient global ischemia in gerbil forebrain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Morphological studies were also performed at the dorsal hippocampal level of coronal sections from the identical brains until 7 days after the reperfusion. Following 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal dentate granule cells at 1 and 3 h of the reperfusion. No histological change was observed in brain cells. Following 5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The induction of HSP70 mRNA in hippocampal CA1 cells sustained until 2 days, while that of HSC70 mRNA declined gradually. Only CA1 cells were lost at 7 days of the reperfusion. Following 15 min of ischemia, the mRNAs were induced in more extensive brain regions including neocortex and thalamic nuclei. In hippocampal CA1 cells, inductions of HSP70 and HSC70 mRNAs diminished by 2 days corresponding with the neuronal damage. HSC70 mRNA induction was not so much as HSP70 mRNA induction especially in hippocampal CA1 and thalamic cells. Our results showed that HSP70 and HSC70 mRNAs were generally induced together after transient ischemia, but that the inductions were spatially and chronologically different after different periods of ischemia. The dissociation of the induction was also found in cells severely injured after 5 and 15 min of ischemia.
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PMID:Temporal profile of the induction of heat shock protein 70 and heat shock cognate protein 70 mRNAs after transient ischemia in gerbil brain. 843 64

A significant dissociation of HSP70 and HSC70 heat shock mRNAs after a 10-min transient forebrain ischemia in gerbil was found only in the hippocampal CA1 neurons which eventually die after the initial ischemic insult, while other hippocampal neurons such as the dentate granule and the CA3 cells which survive ischemia expressed both mRNAs cooperatively. The dissociation was observed as early as after 8 h of reperfusion, a period far shorter than 3-4 days, when the cell death becomes pathologically evident. Thus, the dissociation may serve as a set of early biochemical markers for ischemic neuronal cell death.
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PMID:Dissociation of HSP70 and HSC70 heat shock mRNA inductions as an early biochemical marker of ischemic neuronal death. 847 91

The effect of pentobarbital on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brains was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brains, HSP70 mRNA was scarcely present, whereas HSC70 mRNA was present in most cell populations. After a 5-min occlusion of bilateral common carotid arteries, HSP70 and HSC70 mRNAs were induced together in several cells and were especially dense in hippocampal dentate granule cells at 3 h, but the strong hybridization of the mRNAs continued only in hippocampal CA1 cells by 2 days. At 7 days after the ischemia, CA1 neuronal cell death was apparent, and the HSP70 mRNA disappeared and HSC70 mRNA content returned to the sham level, except for in the CA1 cells. Pretreatment with pentobarbital (40 mg/kg, i.p.) greatly reduced or inhibited the induction of HSP70 and HSC70 mRNAs at both early (3-h) and late (2-day) phases after ischemia. The drug also prevented CA1 cell death at 7 days along with the maintenance of expression of HSC70 mRNA at the sham control level. Hypothermic effects of pentobarbital were noted at 30 and 60 min after the reperfusion, whereas at 2 h there was no statistical significance between the control and drug-treated groups. The great reduction of HSP70 and HSC70 mRNA induction at both early and late phases after ischemia suggests that pentobarbital reduces intra-and/or postischemic stress and may protect CA1 cells from ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain. 851 71

A protective effect of bifemelane hydrochloride (BF) on hippocampal CA1 neuronal death in gerbils was investigated following transient forebrain ischemia in relation to the induction of 70-kd heat shock protein (HSP70) and its mRNA. Histological examination showed that the neuronal density of the hippocampal CA1 sector treated with 10 and 30 mg/kg of BF (i.p.) was higher than that of the vehicle (p < 0.05 and p < 0.01, respectively) at 7 days after ischemia. Immunohistochemistry against HSP70 protein and in situ hybridization for the mRNA revealed that the inductions of immunoreactive HSP70 and the mRNA were remarkably reduced and limited in the brain hippocampi treated with BF (30 mg/kg) as compared with vehicle-treated animals. These data indicate that BF possesses a protective effect against ischemic injury to the vulnerable CA1 neurons. The possible mechanisms of the protection are discussed.
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PMID:Protective effect of bifemelane hydrochloride on ischemic hippocampal CA1 neuronal damage in the gerbil: relation to induction of HSP70. 851 88

Heat shock proteins (HSPs), which have been shown to be induced in the kidney by a variety of stress conditions, including ischemia, inflammation, oxidative stress, and toxin exposure, are believed to protect the cells from injury. In the present study, we demonstrated that administration of vasopressin i.v. to Wistar rats leads to HSP70 induction in the kidney. The effect was specific to the kidney (i.e., absent in brain, heart, lung, muscle, etc.) and selective for the HSP70 gene family (HSP27, HSP60, and HSP90 were not induced). Western blot analysis demonstrated that HSP70 protein expression peaked between 6 and 12 hours after vasopressin administration. Immunohistochemical staining revealed that induction was localized to renal tubule lining cells, with no expression seen in glomerular or interstitial regions. The elevated protein levels were preceded by the induction of HSP70 mRNA within 30 minutes after vasopression injection. The induction of HSP70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the level of transcription. This HSP70 expression was completely blocked in the presence of both a general vasopressin receptor antagonist (V1 and V2 receptors) and an antidiuretic antagonist (V2), but not in the presence of a vasopressor antagonist (V1). These observations could be significant for understanding the possible involvement of HSP70 in physiological processes of the kidney, as well as pathophysiologic conditions associated with either elevated or deficient levels of vasopressin.
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PMID:Vasopressin-induced heat shock protein expression in renal tubular cells. 856 80

In this overview four questions were discussed related to heat shock proteins and myocardial ischemia. Heat shock proteins are chaperones which associate with malfolded proteins and prevent their aggregation into large damaging complexes. In myocardial ischemia, the inducible heat shock protein 70 (hsp70), the mitochondrial heat shock protein 60 and the small 27 heat shock protein increases after 30 minutes of ischemia of the rat heart and subsequent reperfusion. In addition, we describe direct evidence for the protective effect of heat shock proteins against simulated ischemia in H9c2 cells. H9c2 cells are an embryonal rat heart derived permanent cell line which maintains some features of cardiac myocytes. Making stable lines overexpressing the inducible hsp70 we could show that simulated ischemia leads to less injury in H9c2 cells overexpressing the hsp70 transgene. In addition, transgenic mice were constructed in which the rat inducible hsp70 is induced in cardiac myocytes. Submitting such hearts in a Langendorf isolated heart perfusion set-up to 20 minutes of global ischemia and following the contractile recovery of the heart, we found that in transgenic mouse hearts contractile recovery was significantly enhanced. Furthermore in hearts from transgenic mice overexpressing the inducible hsp70, less CK release occurs and infarct size was decreased. In summary, increased expression of the inducible hsp70 exerts a protective effect against the injury induced by myocardial ischemia.
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PMID:Heat shock proteins in myocardial stress. 858 78

p21(WAF1/CIP1/SDI1), an inhibitor of cyclin-dependent kinases, is expressed at varying levels in human adrenal glands removed during surgery or organ recovery. In glands with p21 mRNA, nuclear p21 immunoreactivity, which was occasionally extensive, colocalized with p53 immunoreactivity and DNA damage, as evidenced by in situ end-labeling. Many cells showed morphological features of apoptosis when observed by fluorescent DNA dye staining and electron microscopy. This pattern was also associated with high levels of cytoplasmic heat shock protein 70. To address the question of the origin of p21 expression in some human adrenal glands, rat adrenal glands were subjected to 30 min of ischemia followed by 8 h of reperfusion. Cells with nuclear p21 and p53 appeared in the adrenal cortex together with DNA damage detected by in situ end-labeling. Nuclear p21 immunoreactivity was also produced in adrenal tissue fragments incubated at 37 degrees C in vitro. However, in this case, p21 expression was confined to the cut edge of the tissue. In contrast, p21 in human adrenal glands, as in ischemic rat glands, was within the inner regions of the cortex, supporting an origin of the protein in vivo rather than postmortem. The p53/p21 pathway of reaction to cellular injury, potentially leading to apoptosis, may play a role in tissue damage such as that resulting from ischemia/reperfusion. In the human adrenal cortex this process may be a precursor of adrenal failure.
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PMID:Expression of p21(WAF1/CIP1/SDI1) and p53 in apoptotic cells in the adrenal cortex and induction by ischemia/reperfusion injury. 860 38

Heat shock protein (hsp) induction by stressful stimuli such as heat and ischemia is known to protect cardiac cells from severe stress. The ability to induce hsp's in the heart directly by "nonstressful" means would potentially have important clinical implications. In noncardiac cells, the tyrosine kinase inhibitor herbimycin-A has been shown to induce the 72-kD hsp. We therefore examined whether herbimycin-A and another tyrosine kinase inhibitor, genistein, could induce 70-kD hsp's in primary cultures of rat neonatal cardiomyocytes, and whether these treatments protect against severe stress. Primary cardiomyocytes were incubated with herbimycin-A or genistein. hsp induction was measured 16-20 h later by Western blotting. Cell survival after subsequent lethal heat stress or simulated ischemia was assessed using trypan blue exclusion and released lactate dehydrogenase activity. Our results indicate that, in cardiac cells, herbimycin-A induces 70-kD hsp's but not hsp90, -60, -25, or glucose-regulated protein 78, whereas genistein has no effect on hsp's. Moreover, hsp induction correlated with the ability of herbimycin-A to protect cells against severe stress, whereas genistein has no protective effects. This suggests that herbimycin-A may induce 70-kD hsp's via a tyrosine kinase-independent mechanism. These results indicate the possibility of a pharmacological approach to HSP70 induction and cardiac protection, which may ultimately be of clinical relevance.
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PMID:Specific induction of the 70-kD heat stress proteins by the tyrosine kinase inhibitor herbimycin-A protects rat neonatal cardiomyocytes. A new pharmacological route to stress protein expression? 860 26

Current experimental research on subarachnoid hemorrhage (SAH) has been limited by the lack of a small-animal model that physiologically resembles SAH and consistently demonstrates acute and delayed cellular injury. Recently, a model for inducing SAH by endovascular perforation of the internal carotid artery has been developed in the rat. This model physiologically resembles SAH. However, little histological data detailing cellular injury after SAH are available in this or other models. Using immunocytochemistry, the authors investigated the induction of the 70-kD heat shock protein, HSP70, a sensitive marker for cellular stress or injury in the brain, 1 and 5 days following endovascular SAH. The authors also used the conventional histological techniques of cresyl violet and hematoxylin and eosin staining to investigate cellular damage 1 and 5 days after the endovascular SAH. One day following the SAH, HSP70 was induced in all six animals examined in multiple anatomical regions, including the basal forebrain, thalamus, neocortex, striatum, and hippocampus. This HSP70 induction was observed in multiple vascular distributions bilaterally. Immunostaining with HSP70 occurred primarily in neurons but also was observed in glia and endothelium. Five days after the SAH, a similar but more intense pattern of HSP70 immunostaining was observed in all eight animals examined. Specifically, HSP70 immunoreactivity was observed in at least one region of the hippocampus more often at 5 days (six of eight animals) than at 1 day (one of six animals, p < 0.05, one-tailed Fisher's exact test). No HSP70 immunostaining was observed in control animals at 1 day or at 5 days. Conventional histology demonstrated foci of ischemic neuronal damage and cellular necrosis; however, HSP70 immunocytochemistry detailed cellular injury far better than conventional histology in all animals tested at both 1 day and 5 days. Our results demonstrate that HSP70 is induced in multiple regions and cell types 1 day and 5 days following endovascular SAH. Because ischemia is a known inducer of stress genes, the authors propose that acute and delayed ischemia are the processes responsible for the induction of HSP70 that was observed at 1 day and 5 days, respectively. Investigation of HSP70 induction following endovascular SAH may also serve as the basis for a new, inexpensive animal model to assess potential therapeutic interventions.
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PMID:Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation. 898 6

We studied the temporal profile of nerve growth factor-like immunoreactivity (NGF-LI) in the rat brains following 30 min of middle cerebral artery occlusion. The rats were decapitated at 4 h, 1, 3, 7, and 14 days of recirculation. Brain sections at the level of striatum were immunostained against NGF as well as a stress protein, HSP70. Also, double immunostaining of NGF and glial fibrillary acidic protein was performed. In the sham-control rats, NGF-LI was normally present in the cortical and striatal neurons. However, at 4 h of recirculation, there was a significant decrease of NGF-LI in the ischemic cortex and striatum. From 1 day, NGF-LI was absent completely in the ischemic striatum. However, in the ischemic cortex, NGF-LI decreased to the lowest level at 1 day, but it recovered gradually from 3 days and increased significantly to above sham-control level at 7 days. At 14 days of recirculation, NGF-LI returned to a near sham-control level. In the non-ischemic cortex, NGF-LI increased gradually from 4 h with a peak at 7 days, and returned to the sham-control level at 14 days of recirculation. A HSP70 was induced in the ischemic cortex at 1 and 3 days, when there was a significant reduction of NGF-LI. The number of reactive astrocytes increased gradually and NGF-LI in the reactive astrocytes became gradually intense after ischemia. The present finding showing that NGF-LI can be recovered in the stressed cortical neurons suggests a possible involvement of NGF in the process of neuronal survival after focal cerebral ischemia. The expression of NGF in reactive astrocytes indicates that astrocyte may also play a role in supporting neuronal survival after ischemia.
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PMID:Temporal profile of nerve growth factor-like immunoreactivity after transient focal cerebral ischemia in rats. 872 92


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