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)

The early diagnosis of acute mesenteric occlusion presents a difficult problem in abdominal surgery. In a study on rats the relation between graded small bowel ischemia and the concentration of heme compounds in the plasma was investigated. The ischemia was produced by ligation of terminal vessels at the mesenteric margin of the intestine (mesenteric end arcades) or the superior mesenteric artery. Heme compounds were assayed by a benzidine method developed by Crossby et al. The concentration of heme compounds in the plasma was higher in animals with various grades of intestinal ischemia than in animals subjected to laparotomy alone. This increase was noted as early as 4 hours after induction of moderate and severe grade of ischemia. The results indicate that an increase in plasma concentration of heme compounds takes place at an early stage of moderate and severe small bowel ischemia following mesenteric vascular occlusion but not until after 48 hours in mild ischemia. The clinical value of this method has to be tested in a clinical study.
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PMID:Heme compounds in the plasma in small bowel ischemia in the rat. 126 39

This investigation studies the toxicity of heme proteins and/or their break-down products on renal function. Heme proteinemia precedes acute tubule necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule necrosis. Organic acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by ischemia or obstruction alone. Heme proteinemia in rats or incubation of renal slices in medium containing heme proteins yields several interesting observations. Neither in vivo or in vitro do hemoglobin and methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as hypoxia and elevated ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than hemoglobin or methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that heme proteins play a role in tubule dysfunction seen in acute tubule necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome.
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PMID:Evaluation of the renal toxicity of heme proteins and their derivatives: a role in the genesis of acute tubule necrosis. 541 25

Heme oxygenase (HO-1) gene expression was studied in the brains of rats subjected to 30 min global cerebral ischemia followed by recirculation of up to 24 h. Total RNA was isolated from the cerebral cortex, striatum and hippocampus and reverse-transcribed into cDNA. cDNA was taken as template for PCR using HO-1-specific primers. We found that, when PCR reactions were run for 22 cycles, the amount of PCR products correlated closely with the amount of cDNA. HO-1 gene expression was sharply increased after cerebral ischemia in all three brain structures studied. In the cortex and striatum, the HO-1 mRNA content increased constantly after cerebral ischemia up to 24 h of recovery, being 8- and 9-fold over control after 24 h of recirculation in the cortex and striatum, respectively. In the hippocampus, HO-1 mRNA levels peaked at 4 h after ischemia (9-fold over control) and declined thereafter to 4.5-fold over control 24 h after ischemia. Assuming that the observed increase in mRNA levels is paralled by increased HO-1 protein synthesis, formation of the products of HO reaction, biliverdin and carbon monoxide, is activated after ischemia. These products may produce different and divergent effects on the recovery from the metabolic stress produced by cerebral ischemia.
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PMID:Hemeoxygenase expression after reversible ischemia of rat brain. 787 60

Heme oxygenase is a rate-limiting enzyme in heme catabolism, the end of which include iron, carbon monoxide and bilirubin. Expression of the inducible form of heme oxygenase (HO-1) was investigated in rat brain following 20 min of forebrain ischemia by Northern blot and in situ hybridization analyses. The level of HO-1 mRNA was undetectable in the cerebral cortex of sham control, but increased following ischemic insult, reached the maximum after 12 h of reperfusion, and then decreased. In sham control brain, HO-1 mRNA was detectable only in the scattered neuron-like cells within the dentate gyrus hilus. At 12 h of reperfusion, the remarkable increase in HO-1 mRNA levels was observed in both neuronal and glia-like cells distributed in the neocortex, hippocampus and thalamus.
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PMID:Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia. 788 61

Stressful stimuli such as heat, oxidative stress, heavy metals, and tissue trauma induce the expression of a family of proteins commonly referred to as stress proteins or heat shock proteins. The functions of these proteins are varied but include glycolysis, antioxidant defense, and several postulated "chaperone" functions involving the folding, unfolding, and translocation of other proteins. Heme oxygenase, the enzyme that catalyzes the degradation of heme to biliverdin, is also heat inducible and is, therefore, a heat shock protein. In the kidney, ischemia has been observed by several investigators to induce expression of the more commonly studied heat shock proteins HSP 70 and HSP 72. In addition, exposure of the kidney to myoglobin after glycerol injection induced heme oxygenase. The purpose of this study was to determine whether heme oxygenase is expressed as a stress protein after renal ischemia. Renal ischemia was induced in rats after right nephrectomy by clamping the renal artery for 40 minutes. Gene expression was evaluated after 60 minutes to 96 hours of postischemic reperfusion. There was essentially no expression of heme oxygenase at any of the time points evaluated. The absence of heme oxygenase expression was in striking contrast to the prompt and dramatic expression of HSP 70. This finding is consistent with the concept that all "stress proteins" are not equivalent and that, although there is considerable overlap between heat-sensitive gene promoters and oxidant stress-sensitive gene promoters, there is specificity for the type of stimulus that is able to activate any given stress protein gene.
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PMID:Heme oxygenase is not expressed as a stress protein after renal ischemia. 840 10

Heme oxygenase (HO) isozymes, HO-1 and HO-2 catalyze the cleavage of heme b to form the antioxidant biliverdin IXa, iron and the putative cellular messenger carbon monoxide (CO). Heat and stress have been reported to induce the expression of HO-1, in analogy to ubiquitin, a protein of 8 kDa involved in ATP dependent proteolysis. Earlier, we have shown in anesthetized pigs that brief periods of coronary artery occlusion followed by reperfusion produce prolonged regional cardiac dysfunction (stunning) associated with altered expression of a number of genes. In the present study, we report on a coordinated expression pattern of HO-1 and ubiquitin in the same porcine model in which the left anterior descending coronary artery (LAD) was occluded for 10 min and reperfused for 30 min (group I) and after a second occlusion of 10 min, reperfused for either 30 min (group II) or 90 min (group III) or 210 min (group IV). Myocardial tissue from LAD (stunned) and left circumflex coronary artery (LCx, control) perfused regions were collected in liquid nitrogen and analysed by Northern and dot blot hybridization techniques. We demonstrated a basal myocardial expression of multiple mRNAs (monomer and polymers) encoding ubiquitin and a single mRNA species (1.8 kb) encoding HO-1. However, the expression of both genes was drastically enhanced in the stunned myocardium as compared to the control in groups II and III with maximum mRNAs levels in group II. These results suggest that the myocardial adaptive response to ischemia involves the coordinated induction of HO-1 and ubiquitin, which may be indicative for the existence of a pathophysiologically important defense mechanism whereby, both degradation of denatured cellular proteins and generation of biologically active products of heme metabolism are accelerated.
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PMID:Coordinated expression of heme oxygenase-1 and ubiquitin in the porcine heart subjected to ischemia and reperfusion. 873 36

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxygenase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO-2. HO-1 protein was remarkably induced in brain following ischemia, while the level of HO-2 protein was not noticeably affected. The level of HO-1 protein expression was maximal at 12 h, which is in good agreement with the time course of the HO-1 mRNA induction. In the cortical mantle, most of the cells expressing increased HO-1 protein were identified as pyramidal neurons and astrocytes by their shapes and locations. In hippocampal CA-2 and CA-3 subfields, prominent induction was observed in astrocytes rather than in neuronal cells. By contrast, the HO-1 protein was not detected in the CA1 subfield following the insult, although the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes within the CA1 subfield, there may be an impairment of protein metabolism, preceding the delayed CA1 pyramidal cell losses.
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PMID:Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia. 885 85

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of agents such as heat, heme, and hydrogen peroxide. Evidence suggests that the bile pigments serve as antioxidants in cells with compromised defense mechanisms. Because hypoxia-ischemia (HI) increases the level of oxygen free radicals, the induction of HO-1 expression in the brain during ischemia could modulate the response to oxidative stress. To study the possible involvement of HO-1 in neonatal hypoxia-induced ischemic tolerance, we examined the brains of newborn rat pups exposed to 8% O2 (for 2.5 to 3 hours), and the brain of chronically hypoxic rat pups with congenital cardiac defects (Wistar Kyoto; WKY/ NCr). Heme oxygenase-1 immunostaining did not change after either acute or chronic hypoxia, suggesting that HO-1 is not a good candidate for explaining hypoxia preconditioning in newborn rat brain. To study the role of HO-1 in neonatal HI, 1-week-old rats were subjected to right carotid coagulation and exposure to 8% O2/92% N2 for 2.5 hours. Whereas HO enzymatic activity was unchanged in ipsilateral cortex and subcortical regions compared with the contralateral hemisphere or control brains, immunocytochemistry and Western blot analysis showed increased HO-1 staining in ipsilateral cortex, hippocampus, and striatum at 12 to 24 hours up to 7 days after HI. Double fluorescence immunostaining showed that HO-1 was expressed mostly in ED-1 positive macrophages. Because activated brain macrophages have been associated with the release of several cytotoxic molecules, the presence of HO-1 positive brain macrophages may determine the tissue vulnerability after HI injury.
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PMID:Hypoxia-ischemia, but not hypoxia alone, induces the expression of heme oxygenase-1 (HSP32) in newborn rat brain. 923 21

Heme oxygenase the rate-limiting step in the degradation of heme to bilirubin, generates carbon monoxide. This gaseous molecule plays important roles in neuronal signaling and modulation of vascular tone. Additionally, carbon monoxide is involved in some pathological conditions (e.g., ischemia, endotoxic shock, excitotoxicity) as a protective or toxic factor. Bilirubin, another heme metabolite, exhibits intriguing biological activities as an antioxidant, an antimutagen, and an anti-complement agent. Vital functions and the dual nature displayed by these two heme metabolites are discussed.
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PMID:New physiological importance of two classic residual products: carbon monoxide and bilirubin. 925 78

Heme oxygenase (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that induce oxidative injury such as hemoglobin/heme, hypoxia-ischemia and cytokines. Overexpression of HO-1 in endothelial cells (EC) might, therefore, protect against oxidative stress produced under these pathological conditions, by generation of CO, a vasodilator, and bilirubin, which has antioxidant properties that enhance blood vessel formation to counteract hypoxia-induced injury. A plasmid containing the cytomegalovirus promoter (pCMV) neomycin human HO-1 gene complexed to cationic liposomes, lipofectin, was used to transfect rabbit coronary microvessel EC. Cells transfected with human HO-1 gene demonstrated a twofold increase in HO activity and maintained a similar phenotype as in the nontransfected cells. Cell number in transfected cells with human HO-1 gene increased by about 45%, as compared to nontransfected or those transfected with control pCMV. Transfected and nontransfected EC revealed a similar response to basic fibroblast growth factor (bFGF) in capillary formation. However, transfected cells with the human HO-1 gene exhibited a twofold increase in blood vessel formation. The angiogenic response of EC to overexpression of HO-1 gene provides direct evidence that the inductive form of HO-1 following injury represents an important tissue adaptive mechanism for moderating the severity of cell damage produced in inflammatory reaction sites of hemorrhage, thrombosis and hypoxic-ischemia. Thus, HO-1 may participate in the regulation of EC activation, proliferation and angiogenesis.
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PMID:Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis. 940 20


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