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)

Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos, c-jun, and growth factors. It indicates that the mechanism of ischemic tolerance involves a cascade of events including liberation of adenosine, stimulation of adenosine A1 receptors, and, via these receptors, opening of sulfonylurea-sensitive ATP-sensitive K+ channels.
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PMID:Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. 775 61

The expression of interleukin-6 (IL-6) mRNA in the focal ischemic rat cortex was studied by means of Northern hybridization. IL-6 mRNA was induced after permanent occlusion of the middle cerebral artery, reached a significant level at 3 h, and peaked at 12 h, i.e., approximately 10-fold increase in the ischemic zone compared with the nonischemic cortex or sham-operated controls. The increased IL-6 mRNA was elevated for at least 24 h. Low levels of IL-6 mRNA were detected in sham-operated rats or in the contralateral nonischemic cortex. The expression of c-fos and zif268 mRNAs, two early response genes, was rapid (increased by 1 h postischemia) and transient (returned to basal levels by 24 and 12 h, respectively), clearly having different kinetic patterns from that of IL-6 mRNA. The early response kinetic pattern of c-fos and zif268 mRNAs in focal ischemia suggests their transcriptional regulatory roles in response to ischemic insult, while the delayed induction pattern of IL-6 mRNA suggests a role for this pleiotropic cytokine in the inflammatory response to the focal ischemic damage of the brain.
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PMID:Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. 779 34

Levels of mRNAs encoding the proto-oncogene, c-fos, and the 70 kDa stress protein, hsp70, were evaluated in gerbil brain following transient cerebral ischemia of varied duration by in situ and blot hybridization techniques. Blots of total hippocampal RNA obtained after 5 min ischemic insults confirmed a characteristic, transient time course of c-fos expression with a striking elevation within 1 h and a return to control levels by 3 h recirculation. Hsp70 hybridization was significant at 1 h and continued to increase until 3-6 h after the insult. Striking accumulation of c-fos mRNA was detected within 15 min recirculation in dentate granule cells, persisting through 1 h, and a weaker signal was evident in CA1 and CA3 pyramidal neurons of hippocampus, as well as in prepiriform/entorhinal cortex and neocortical regions, during the same interval. Hsp70 hybridization showed an identical distribution at 1 h recirculation. Ischemic insults of 1 min duration resulted in no detectable increase of either mRNA, while 2 min ischemia resulted in changes comparable to those seen after 5 min insults. This common threshold corresponds to the ischemic interval required for energy depletion and resultant failure of intracellular ion homeostasis. In contrast, expression of hsp70 mRNA was not observed under conditions of brief depolarization accompanying cortical or hippocampal spreading depression that were shown to induce c-fos. A delayed component of c-fos mRNA expression was not detected in this model, while persistent hsp70 hybridization, restricted to hippocampal CA1 neurons, was evident at 48 h after either 2 min or 5 min ischemic insults. The parallels in c-fos and hsp70 mRNA expression during early recirculation suggest that overlapping mechanisms triggered following postischemic depolarization contribute to their induction after transient ischemia.
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PMID:Coexpression of c-fos and hsp70 mRNAs in gerbil brain after ischemia: induction threshold, distribution and time course evaluated by in situ hybridization. 785 54

The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.
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PMID:Differential expression of c-jun, c-fos and hsp 70 mRNAs after folic acid and ischemia-reperfusion injury: effect of antioxidant treatment. 792 67

Left ventricular hypertrophy (LVH) is an important independent risk factor for cardiovascular morbidity and mortality. Initially LVH improves contractility and pump function; however, over time a sequence of events occurs including disintegration of myofibrils, interstitial fibrosis, adenosine triphosphate depletion, and altered gene expression. Eventually the hypertrophied myocardium outgrows its capillary bed, subendocardial ischemia develops, and the heart fails. Hemodynamic (pressure) and nonhemodynamic signals (catecholamines, angiotensin II, thyroid hormone) have been identified that stimulate hypertrophic growth of the myocardium. Evidence is also accumulating that the induction of immediate early genes such as c-fos and c-myc may participate in the development of LVH.
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PMID:Cellular and signaling mechanisms of cardiac hypertrophy. 793 62

The protein products of the immediate early genes (IEG)s have been proposed to play an important role in long-term tissue plasticity such as cell repair or programmed cell death. The expression of liver IEGs was studied following liver ischemia (LI) or OLT in rats. In LI, 60 min of warm ischemia was induced in shunted rats (shunt LI group; 100% survival) and nonshunted rats (nonshunted LI group; poor survival). In OLT, donor livers were transplanted into the recipients within 1 hr (fresh liver OLT group; 100% survival) or after 24 hr of storage using University of Wisconsin solution (preserved liver OLT group; poor survival). Using both models, IEG mRNAs (c-fos and c-jun) were analyzed by Northern blot hybridization at various times before and after reperfusion. The expression of liver IEGs was not induced by warm ischemia and cold preservation alone. Reperfusion of livers following warm ischemia or cold preservation resulted in a distinctly different pattern of gene expression in viable and nonviable livers. In shunted LI and fresh liver OLT groups (viable), c-fos and c-jun mRNAs increased markedly to a peak value within 1-2 hr of reperfusion, returning to basal level by 3 hr. In nonviable livers, the level of these mRNAs was detected continuously at 3 hr of reperfusion in the nonshunted LI model and also at 6 hr after reperfusion in the preserved liver OLT group. Our data suggest that a protracted pattern of expression of c-fos and c-jun in the liver at the early stage of reperfusion might be correlated with the severity of liver transplant-related insults and subsequent graft failure.
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PMID:The induction of immediate early genes in postischemic and transplanted livers in rats. Its relation to organ survival. 794 Jul 19

Injuries to the brain induce rapid expression of c-fos and c-jun proto-oncogenes in neurons. The protein products (Fos and Jun) of these cellular immediate early genes are thought to regulate target genes that participate in fundamental biological responses. In recent studies of rat brain infarct we demonstrated that gliosis and angiogenesis, two of the fundamental biological responses, are related to neuronal expression of basic fibroblast growth factor (bFGF). In the present study, we explore the linkage between c-fos and bFGF genes by comparing the temporal and spatial domains of Fos and bFGF immunoreactivities (IR) in brain infarct and in transient global ischemia. We demonstrate colocalization of Fos-IR and ischemic changes in neurons at infarct periphery and in regions of "selective vulnerability" beginning 3 hours post-infarction and lasting up to 1-2 weeks. These are: cortical neurons in layers II-III and V, interneurons in hippocampal formation, cerebellar Purkinje cells, and many subcortical nuclei and brainstem nuclei. bFGF-IR appears 12-24 hours later than Fos-IR in the same region but in non-ischemic neurons and the expression persists beyond 2 weeks. Persistent and not transient c-fos expression appears to be associated with ischemic neuronal death, although some of these neurons may survive beyond 2 weeks postinfarction.
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PMID:c-fos protein expression and ischemic changes in neurons vulnerable to ischemia/hypoxia, correlated with basic fibroblast growth factor immunoreactivity. 796 1

In aged individuals the incidence of heart failure is higher than in younger subjects. Ischemic events are also common in the aged heart because of changes in the coronary vasculature and myocytes caused by aging. Adaptational responses to increased hemodynamic overload and to ischemia in the aged heart are discussed at the molecular, cellular and organ levels. One characteristic of the aged heart is a limited capacity for adaptation with hypertrophy to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun by hemodynamic stress. This diminution results from the aging of the heart per se and may be modulated by extracardiac factors. An age-related diminution was also observed in the mRNA induction of heat shock proteins by transient ischemia. However, this diminished induction of immediate early genes in the aged heart was not observed after more severe stress. With regard to the coronary vasculature, the age at which pressure-overload begins seems to be one of the important factors which determine the vascularity of hypertrophied hearts. Late-onset pressure-overload decreased dilator reserve in spite of the absence of myocardial hypertrophy. Thus, the responses to stress in the aged heart are quite different from those in the young heart. The limited capacity for adaptation to hemodynamic overload and poor protective mechanisms against stress may be causes of the higher incidence of heart failure in the aged.
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PMID:Responses to hemodynamic stress in the aged heart. 796 46

Middle cerebral artery (MCA) occlusion in halothane-anesthetized rats induced c-fos, junB, and c-jun immediate early gene mRNAs and hsp70 heat shock gene mRNA in brain. In situ hybridization studies showed that c-fos and junB were induced throughout all of the cortex at 1 and 4 h following MCA occlusion. hsp70 was induced in the core and margins of the MCA ischemia. By 24 h, there was little expression of c-fos, junB, c-jun, and hsp70 in the core of the MCA infarct; there was modest induction of hsp70 at the margins of the infarct; and there was diffuse induction of c-fos, junB, and c-jun in all of the cortex outside the infarct. MCA occlusion also induced these genes in subcortical structures. c-fos, junB, and hsp70 were induced in ipsilateral medial striatum, most of thalamus including medial and lateral geniculate nuclei, substantia nigra, and hippocampus. Most of these structures, except for the striatum, are not supplied by the MCA. These data show that changes in gene expression can occur in regions remote from an infarction.
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PMID:Induction of c-fos, junB, c-jun, and hsp70 mRNA in cortex, thalamus, basal ganglia, and hippocampus following middle cerebral artery occlusion. 806 76

Regional and global myocardial ischemia and reperfusion have been demonstrated to induce expression of the stress response protein heat shock 70 (HSP70) and of immediate early genes, c-jun, c-fos, and c-myc. Because of the models that have been utilized, it has not been possible to discriminate whether this response is the consequence of ischemia, reperfusion, or abnormal hemodynamic stress superimposed on stunned myocardium. In a nonworking isolated and blood-perfused rat heart model, we evaluated the mRNAs for c-fos, c-myc, and hsp70. The heart was subjected to varying periods of ischemia and reperfusion. Significant increases in hsp70 and c-fos were observed, which increased with longer periods of ischemia. No significant increase in c-myc was measured. In addition, mRNA encoding the Ca2+/glucose responsive stress protein GRP78 was evaluated. No increase in this early response gene was noted despite the use of a model associated with cellular calcium loading. Based on these observations, we suggest that the induction of hsp70 and c-fos is the consequence of ischemia and reperfusion and not dependent upon an early hypertrophy response such as would be observed in afterload mismatching or on calcium loading. Further investigations are necessary to isolate the effects of ischemia from those of reperfusion.
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PMID:Myocardial stunning: association with altered gene expression. 806 49


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