Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
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PMID:Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain. 154 93

hsp26, the small heat shock protein of Saccharomyces cerevisiae, accumulates in response to heat and other types of stress. It also accumulates during the normal course of development, as cells enter stationary phase growth or begin to sporulate (S. Kurtz, J. Rossi, L. Petko, and S. Lindquist, Science 231:1154-1157, 1986). Analysis of deletion and insertion mutations demonstrated that transcriptional control plays a critical role in regulating HSP26 expression. The HSP26 promoter was found to be complex and appears to contain repressing elements as well as activating elements. Several upstream deletion mutations resulted in strong constitutive expression of HSP26. Furthermore, upstream sequences from the HSP26 gene repressed the constitutive expression of a heterologous heat shock gene. We propose that basal repression and heat-induced depression of transcription play major roles in regulating the expression of HSP26. None of the recombinant constructs that we analyzed separated cis-regulatory sequences responsible for heat shock regulation from those responsible for developmental regulation of HSP26. Depression of HSP26 transcription may be the general mechanism of HSP26 induction in yeast cells. This regulatory scheme is very different from that described for the regulation of most other heat shock genes.
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PMID:Transcriptional derepression of the Saccharomyces cerevisiae HSP26 gene during heat shock. 212 93

It has been appreciated for many years that the recovery of brain protein synthesis activity following a transient ischemic insult lags considerably behind the normalization of brain energy metabolism. More recently, selective increases or decreases in the synthesis of specific proteins have been documented to occur during postischemic recirculation, the best characterized of such changes being the induction of proteins characteristic of the "heat shock" or "stress" response. This review will summarize these developments in the study of changes in gene expression following ischemia, with an emphasis on regional differences in the vulnerability of overall translational activity as well in the expression of stress proteins and their mRNAs. The neuronal localization of the 70 kDa heat shock protein, hsp70, after ischemia is contrasted with its largely glial and vascular induction following a hyperthermic stress. The lasting depression of protein synthesis and sustained expression of hsp70 mRNA in vulnerable hippocampal CA1 neurons appear to be mechanistically related and may constitute markers for cellular pathophysiology leading to neuronal cell loss. Elucidating the mechanisms responsible for cell-specific regulation of stress proteins and other gene products may eventually contribute to a more precise understanding of the evolution of brain injury at the molecular level following diverse insults.
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PMID:Protein synthesis and the heart shock/stress response after ischemia. 227 46

Cortical spreading depression (CSD) was induced in male Wistar rats by applying 2 M KCl to the frontal cortex of one hemisphere for 2 h. Saline was applied to the contralateral cortex in the same manner. Following recovery for 24 h, bilateral forebrain ischemia was induced for 6 min, and the animals were permitted to survive for 6 days for assessment of histopathology. The number of necrotic neurons was counted in the cerebral cortex, striatum, and hippocampus of both hemispheres. In separate sets of animals, the effects of KCl application on cortical direct current (DC) potential and regional expression of c-fos mRNA and 72-kDa heat shock protein (hsp72) mRNA were determined. Forebrain ischemia induced selective neuronal necrosis in both hemispheres, but the number of necrotic neurons in the cerebral cortex ipsilateral to the application of KCl was significantly smaller than that in the contralateral cortex (p < 0.02, Wilcoxon signed rank test, n = 7). In the striatum and hippocampus, there were no significant differences in neuronal necrosis between hemispheres. Application of KCl for 2 h induced 11 +/- 2 (mean +/- SD, n = 5) negative deflections of DC potential in the ipsilateral cortex; none were detected in the contralateral cortex. Widespread expression of c-fos mRNA was evident in the ipsilateral cortex, while hsp72 mRNA expression was restricted to the KCl application site. The present results demonstrate that CSD induces tolerance of cortical neurons to ischemia by mechanisms unrelated to hsp72.
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PMID:Spreading depression induces tolerance of cortical neurons to ischemia in rat brain. 767 67

Repeated brief ischemic episodes result in prolonged depression of contractile function despite the absence of irreversible damage, a phenomenon called myocardial stunning. Considerable evidence exists to suggest that oxygen radicals, particularly the hydroxyl radical formed as a result of Fenton reaction or nitric oxide-peroxynitrite pathway, may contribute to the pathogenesis of myocardial stunning. The generation of free radicals may cause sarcoplasmic reticulum dysfunction, and both of these mechanisms may lead to calcium overload, which in turn could exacerbate the damage initiated by oxygen radicals. Antioxidant therapy has been shown to effectively attenuate or even prevent the development of prolonged depression of contractility in many studies. In addition, preconditioning with brief ischemic insults is able to trigger protection, which appears to attenuate stunning 24 to 48 hours later. The mechanism of this protection is not known, although one or more members of the heat shock protein family may have a role in protection against stunning.
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PMID:Free radicals, calcium homeostasis, heat shock proteins, and myocardial stunning. 767 33

There is compelling, although indirect, evidence that oxygen free radicals, generated during ischemia as well as upon reperfusion and reoxygenation of the ischemic heart, contribute to the reversible ventricular dysfunction characterized as myocardial stunning. Evidence of cell membrane damage as well as depression of sarcoplasmic reticulum and mitochondrial function with resulting calcium overload of the cell may be a result of lipid peroxidation of the cell by free radical products. Radical scavenger enzymes have been shown to greatly reduce the appearance of mRNA of a stress response protein (heat shock protein 71) in a pig heart model of stunning. The potential role for the introduction of antioxidant enzymes or stress protein in the cell is presented as a possible strategy for attenuating free radical damage during postischemic reflow.
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PMID:Oxygen radicals and myocardial stunning. 806 31

The effects of electroconvulsive seizure and anti-convulsant drugs on induction of mRNA of heat shock protein were studied in mouse brain. Electrical shock induced mRNA of heat shock cognate protein (HSC70), but not heat shock protein (HSP70) mRNA. The induction was maximum 1 h after the ECS and continued for several hours, followed by long-lasting depression. Diazepam slightly prevented the ECS, but strongly attenuated the induction of HSC70 mRNA. Whereas phenytoin, which blocked the seizure, did not decrease but delayed the induction of HSC70 mRNA. The present results suggest that HSC70 mRNA level is increased with the ECS and that the induction level did not necessarily correlate the severity of the seizure.
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PMID:Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain. 823 52

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

We investigated the temporo-spatial expression of astrocyte glial fibrillary acidic protein (gfap) and sulfated glycoprotein 2 (sgp-2) mRNAs in comparison to 70-kDa heat shock protein (hsp70) mRNA by in situ hybridisation in rats subjected to permanent occlusion of the middle cerebral artery (MCA). Gfap mRNA started to increase in the cingulate cortex of the lesioned hemisphere 6 h after MCA occlusion and gradually spread over the lateral part of the ipsilateral cortex and the striatum from 12 h to 3 days, peaking at 3 days after MCA occlusion. Gfap mRNA also increased in the contralateral cingulate cortex and corpus callosum at 12 and 24 h. Hsp70 mRNA increased markedly in the ipsilateral cortex adjacent to the ischemic lesion, and slightly within the lesion area from 3 to 24 h and disappeared after 3 days. By 7 days, gfap and sgp-2 mRNAs were increased markedly in the peri-infarct area, and in the ipsilateral thalamus parallel with the delayed neuronal damage, whereas the widespread increase of gfap mRNA in the ipsilateral hemisphere declined. Post-occlusion treatment with the glutamate receptor antagonists MK-801 and NBQX slightly attenuate the induction of gfap but did not qualitatively affect the topical expression pattern. Within the cingulate cortex MK-801 treatment resulted in a significant decrease of the signal intensity at all survival times, reflecting most likely an attenuation of lesion-induced spreading depression like depolarization waves by MK-801. The area of hsp70 expression was reduced by both MK-801 and NBQX, most likely reflecting the decrease of the lesion area by both treatment regimens. Our study thus revealed an early and widespread increase of gfap mRNA in the non-ischemic area including the contralateral hemisphere starting between 3 and 6 h, and a delayed circumscribed expression in the peri-infarct border zone after 1 week. Comparison with the expression of hsp70 mRNA suggests that the absence of an early gfap mRNA induction in the peri-lesion zone reflects an impairment of astrocytic function which may be of importance for infarct growth during the early evolution of the pathological process.
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PMID:Monitoring the temporal and spatial activation pattern of astrocytes in focal cerebral ischemia using in situ hybridization to GFAP mRNA: comparison with sgp-2 and hsp70 mRNA and the effect of glutamate receptor antagonists. 891 67

The short-term cardiac side effects of 2',3'-dideoxycytidine (ddC, zalcitabine) were studied in rats in order to understand the biochemical events contributing to the development of ddC-induced cardiomyopathy. In developing animals, ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by prolonged RR, PR, and QT intervals and J point depression. The energy metabolism in the heart was compromised, characterized by a decreased creatine phosphate/creatine ratio (from 2.05 normal value to 0.75) and a decreased free ATP/ADP ratio (from 332 normal value to 121). The activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase) also decreased significantly. Southern blot and polymerase chain reaction analysis did not show deletions or a decrease in the quantity of mitochondrial DNA (mtDNA) deriving from ddC-treated rat hearts, indicating that under our experimental conditions, ddC-induced heart abnormalities were not the direct consequence of mtDNA-related damage. The ddC treatment of rats significantly increased the formation of reactive oxygen species (ROS) in heart and skeletal muscle as determined by the oxidation of non-fluorescent dihydrorhodamine123 to fluorescent rhodamine123 and the oxidation of cellular proteins determined from protein carbonyl content. An activation of the nuclear poly-(ADP-ribose) polymerase (EC 2.4.2.30) and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals. A decrease in the quantity of heat shock protein (HSP)70s was also detected, while the level of HSP25 and HSP60 remained unchanged. Surprisingly, ddC treatment induced a skeletal muscle-specific decrease in the quantity of three proteins, one of which was identified by N-terminal sequencing as myoglobin, and another by tandem mass spectrometer sequencing as triosephosphate isomerase (EC 5.3.1.1). These data show that the short term cardiotoxicity of ddC is partially based on ROS-mediated signalling through poly- and mono-ADP-ribosylation reactions and depression of HSP70 levels, whose processes represent a new mtDNA independent mechanism for ddC-induced cell damage.
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PMID:Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions. 1059 Nov 46


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