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

Fibroblast growth factors (FGF) and type beta-1 transforming growth factor (TGF beta 1) are pleiotropic regulatory peptides which are expressed in myocardium in a precise developmental and spatial program and are up-regulated, in the adult heart, by ischemia or a hemodynamic burden. The accumulation of trophic factors after aortic banding supports the hypothesis that autocrine or paracrine pathways might function to mediate, in part, the consequences of mechanical load. Our laboratory has demonstrated that cardiac muscle cells are targets for the action of peptide growth factors and, more specifically, that modulation of the cardiac phenotype by basic FGF (bFGF) and TGF beta 1 strongly resembles the induction of fetal cardiac genes--including skeletal alpha-actin (SkA), beta-myosin heavy chain, and atrial natriuretic factor--which are characteristic of pressure-overload hypertrophy. Unexpectedly, and despite effects like those of bFGF on five other cardiac genes, acidic FGF (aFGF) was found to repress, rather than stimulate, SkA transcription in neonatal cardiac muscle cells. The proximal 200 nucleotides of a heterologous SkA promoter were sufficient for basal tissue-specific transcription, for induction by bFGF, and for inhibition by aFGF. Thus, both positive and negative regulation by peptide growth factors can be localized to the proximal SkA promoter. Full promoter activity required each of three CC[A/T]6GG motifs similar to the serum response element (SRE) for activation of the c-fos proto-oncogene, as previously shown for SkA transcription in a skeletal muscle background. The most proximal SRE, SRE1, was sufficient in the absence of other SkA promoter sequences for efficient tissue-specific expression in cardiac myocytes (versus cardiac fibroblasts), and was stimulated by bFGF to the same extent as the full-length promoter and endogenous gene. Despite its ability to repress the SkA promoter, aFGF had no significant effect on SRE1. Both FGFs up-regulated the canonical fos SRE, to a comparable degree. Thus, SRE1 can discriminate between signals generated in cardiac myocytes by bFGF and aFGF. In cardiac myocyte extracts, two predominant proteins contact SRE1: serum response factor (SRF) and a second protein, F-ACT-1. Thus, serum response factor and F-ACT-1 are candidate trans-acting factors for basal transcription of the SkA gene in cardiac muscle cells and for induction of SkA by bFGF and, potentially, other trophic signals.
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PMID:Growth factors, growth factor response elements, and the cardiac phenotype. 128 69

Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia-ischemia in immature rat brain. 140 Jun 53

The c-fos proto-oncogene is activated by transient cerebral ischemia. This activation may signify a specific genetic response to ischemia affecting tolerance to ischemia and ultimate cell survival. Hyperglycemia, which enhances brain injury from transient ischemia, was studied for its effects on this gene system in gerbils by measuring c-fos mRNA 2 h after 20 min of bilateral carotid artery occlusion. Brain c-fos mRNA was increased by ischemia (11.7 +/- 5.0, p less than or equal to 0.05, fold increase) compared to nonischemic controls (1.0 +/- 1.3). Pretreatment with 1 g/kg of glucose partially reduced postischemic c-fos mRNA (6.3 +/- 1.6, p less than or equal to 0.05) while 4 g/kg of glucose completely suppressed postischemic c-fos expression (0.7 +/- 0.3, p less than or equal to 0.05). These data indicate that hyperglycemia suppresses normal postischemic gene expression and suggest the possibility that such suppression is a predictor or even a contributor to hyperglycemia-enhanced ischemic brain damage.
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PMID:Hyperglycemia suppresses c-fos mRNA expression following transient cerebral ischemia in gerbils. 172 38

Early induction of the mRNAs encoding the c-Fos and c-Jun nuclear proteins was examined in rat brain by in situ hybridization at various timepoints following global forebrain ischemia by the method of four-vessel occlusion. All animals were subjected to 20 min of transient ischemia. This produced a pattern of proto-oncogene activation that was most intense in the granule cells of the dentate gyrus 30 min after ischemia, while the hilar cells in the dentate and the pyramidal cells of the CA3 region in the hippocampus showed a more delayed but robust expression of these immediate early genes at 1 h. The neurons of the CA1 region exhibited a more moderate hybridization signal at 1-2 h postischemia. Very little hybridization signal for either immediate early gene could be detected in animals perfused with fixative immediately following ischemia, suggesting that cellular energy levels may have to be restored to a certain level before efficient de novo mRNA synthesis can occur. In the cerebellum, a similar temporal pattern was observed: the granule cells exhibited a prompt but patchy expression of c-fos and c-jun that was followed by a delayed signal in the Purkinje cells. Without exception c-fos and c-jun appeared to be expressed in unison, although the time course of c-fos and c-jun mRNA accumulation and decay was different in various brain regions: invariably the cerebellum returned rapidly to its baseline with virtually no remaining signal at 3 h postischemia, while c-fos and c-jun activation in the hippocampus remained high at 3 h and returned to baseline by 6 h. Several other brain regions showed early production of c-fos and c-jun mRNAs, such as the medial habenula, piriform cortex, the amygdala, the centromedian, lateral posterior, paracentral, intermediodorsal and reuniens nuclei of the thalamus and the ventromedial and dorsal nuclei of the hypothalamus; in the brainstem, the trapezoid body and the noradrenergic neurons of the locus ceruleus as well as the adrenergic neurons in the ventrolateral medulla (C1 group) and nucleus tractus solitarius (C2 group) regions displayed slightly less intense hybridization signals. In addition, the ependyma of the lateral ventricles and the third ventricle showed a prompt albeit short-lived production of c-fos and c-jun mRNAs. Sham-operated animals as well as animals that had survived to one week postischemia showed either no or only trace levels of hybridization signal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia. 181 28

Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of proto-oncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury.
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PMID:Differential gene expression in the recovery from ischemic renal injury. 191 Jan 24

In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemic models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemic insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemic insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfield appears to be reversible and returns to the normal level 12 days following the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells. 206 47

Induction of messenger RNA encoding the 70-kDa heat shock or stress protein, hsp70, and the product of the proto-oncogene c-fos was evaluated in gerbil hippocampus by in situ hybridization at various recirculation intervals after 5 minutes of ischemia. Striking increases in c-fos RNA were observed in dentate granule cells within 15 minutes of recirculation and remained evident through 1 hour, returning to undetectable control levels by 3 hours. Modest c-fos hybridization was seen in CA1 and CA3 neurons during the same time course. These results are consistent with the rapid and transient stimulation-induced c-fos expression observed in many experimental systems. Hsp70 expression showed a longer time course, being strongly induced in all major hippocampal neuron populations within 3 hours and persisting for approximately 12 hours in dentate granule cells and through 24 hours in CA3 pyramidal neurons. Notably, the most prolonged expression of hsp70 RNA was observed in vulnerable CA1 neurons that minimally accumulate the immunoreactive protein, with hybridization detected essentially until the death of this cell population at 3-4 days. These studies demonstrate an overlapping distribution of hsp70 and c-fos expression in gerbil hippocampus after ischemia, although there are differences in time course and in the relative induction observed in different neuron populations. The transient increase in c-fos hybridization in dentate granule cells is identical to that seen in various seizure paradigms and provides further support for activation of hippocampal circuitry after ischemia. The prolonged time course of hsp70 messenger RNA expression in vulnerable CA1 neurons may provide a molecular correlate of proposed excitotoxic mechanisms mediating delayed neuronal death.
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PMID:70-kDa heat shock protein and c-fos gene expression after transient ischemia. 212 54

Temporary renal ischemia is followed by increased DNA synthesis and cell division as the kidney restores the continuity of the renal epithelium. We sought to characterize some of the changes in proto-oncogene and growth factor expression during this proliferative response. Northern analysis of polyadenylated RNAs of kidney cortical and outer stripe of outer medullary tissue from male Sprague-Dawley rats was performed following release of renal hilar clamping of 50 minutes duration. Ischemia produced an increase in c-fos mRNA that reached a peak at one hour and declined rapidly to control levels by four hours after release of the clamp. A similar rapid increase and decrease in early growth response 1 (Egr 1) mRNA was noted. The response of these immediate early genes was typical of their response to mitogens, suggesting that they served a similar role in renal cell regeneration. Levels of c-Ki-ras and glyceraldehyde phosphate dehydrogenase mRNA were unchanged. Renal preproEGF mRNA decreased at two hours, was virtually absent by 24 hours and remained low for at least four days after ischemia. Urinary excretion of EGF fell immediately after release of ischemia and before the decline in preproEGF mRNA or SNGFR, suggesting post-transcriptional affects of ischemia on renal EGF production. EGF excretion returned to only 50% of control by day 21. Specific 125I-EGF binding increased in membrane fractions of cortex, outer medulla and inner medulla as early as 24 hours after release of the clamp. Cortical 125I-EGF binding increased in the proximal tubule but not in the glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in gene expression after temporary renal ischemia. 236 5

The amounts of mRNAs for proto-oncogene c-fos and structural protein beta-actin were measured in the rat cerebral cortex after transient forebrain ischemia. A transient and specific induction of c-fos mRNA was noticed in the cerebral cortex 30-90 min after ischemia followed by decline to control value. In contrast, the level of mRNA for beta-actin was not altered throughout the recirculation period examined. These results suggest specific role of c-fos gene after brain damage.
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PMID:Proto-oncogene c-fos is transiently induced in the rat cerebral cortex after forebrain ischemia. 249 62

Expression of the proto-oncogene bcl-2 prevents programmed cell death in vitro, but it is not known whether bcl-2 plays a role in determining cell survival after cerebral ischemia. Using immunohistochemistry and Western blot analysis, bcl-2 protein expression was studied in the rat brain 24 h following 60 or 120 min of temporary focal ischemia. Sixty minutes of ischemia induced bcl-2 protein in neurons throughout the frontoparietal cortex in non-infarcted regions, whereas 120 min of ischemia induced bcl-2 in neurons only just outside the margin of the infarction. bcl-2 protein was also induced in glial cells, mainly microglia, border zone of the infarction. In the infarcted regions of caudate and cortex, bcl-2 protein was exclusively induced in endothelial cells and the vessel walls. Western blot revealed a characteristic single band at 26 kDa only in ischemic samples. These data show that bcl-2 is induced in sublethally injured cells and suggest that bcl-2 could play a role in determining cell survival in cerebral ischemia.
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PMID:bcl-2 is expressed in neurons that survive focal ischemia in the rat. 775 35


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