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

Liver injury by 30-min ischemia following reperfusion was examined biochemically and histopathologically. A greater increase in the level of LDH was observed after 1-hr reperfusion. However, the level of LDH decreased in proportion to the period of reperfusion, while the levels of GOT and GPT were also increased rapidly and reached its peak at 12 hr following reperfusion and were almost restored to the control level by 48 hr. A similar increase was obtained in the lipid peroxides of the liver. In addition, cyt. P-450 content and NADPH cyt. c reductase activity decreased in proportion to the period of reperfusion up to 12 hr and then recovered by 96 hr. On the other hand, heme oxygenase activity was significantly increased by ischemia-reperfusion. The ischemia-reperfused liver resulted in various morphological changes with the period of reperfusion. The destruction of Disse's space, vacuolization of the cytoplasm and nonviable hepatocytes were observed after 12-hr reperfusion. These results indicate the greatest damages of the liver induced by 30-min ischemia following reperfusion is observed after 12-hr or 24-hr reperfusion. The liver injury by ischemia-reperfusion could be a useful experimental model to develop for future studies.
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PMID:[An injury of the liver caused by ischemia-reperfusion in rat liver. Report 2: Relationship between the damage of the liver and during the period of reperfusion]. 146 2

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

Presently we describe, for the first time, induction of microsomal heme oxygenase-1 (HO-1) mRNA and protein in response to ischemia/reperfusion and therefore define HO-1 as stress protein in the kidney. Specifically, Northern blot analysis of kidneys of rats subjected to bilateral ischemia for 30 min revealed an increase of 8- to 10-fold in the level of 1.8 Kb HO-1 mRNA 6 hr after reperfusion. The increase in transcript level was maintained when assessed after 24 hr. The levels of 1.3 and 1.9 Kb transcripts for the second isozyme of HO, HO-2, were decreased at both time points. The increase in HO-1 mRNA was reflected in HO-1 protein level, as judged by Western blot analysis and at the level of activity as judged by the rate of bilirubin formation. An absence of change in adrenal HO-1 mRNA level subsequent to renal ischemia/reperfusion suggested that the induction of kidney HO-1 did not reflect a generalized response of the rat organs to stress; rather, it was a target organ specific response. Moreover, in kidneys subjected to ischemia 6 and 24 hr after reperfusion, significant increases in the cellular content of heme were observed; heme is a known inducer of HO-1 synthesis. Ischemia/reperfusion also adversely affected concentration of cytochrome P-450 in both mitochondrial and the microsomal fractions of the kidney. We suggest that increase in tissue heme levels may be a significant factor in damage caused by ischemia/reperfusion to renal tissue, whereby the metalloporphyrin promotes oxygen-free radical formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. 842 44

The anti-oxidative effect of bilirubin was investigated in an ischemia-reperfusion model of rat liver. The rat portal vessel and liver artery were ligated with a vascular clip, and after reperfusion the urine was collected at intervals. The amount of biopyrrins, the oxidative metabolites of bilirubin, in rat urine reached a maximum 4 hours after reperfusion. Biotripyrrin-a and -b which are biopyrrins isolated from human urine were included in urinary bilirubin oxidative metabolites of rats after reperfusion. The hepatic mRNA level of heme oxygenase-1 (HO-1), the rate limiting enzyme of bilirubin biosynthesis, reached a maximum after 4 hours. Furthermore, the hepatic activity of HO began to rise 4 hours after treatment and remained high until 24 hours posttreatment. These findings suggest that bilirubin acts as a physiological antioxidant in vivo in ischemia-reperfusion and that bilirubin biosynthesis is evoked by oxidative stress.
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PMID:Role of bilirubin as an antioxidant in an ischemia-reperfusion of rat liver and induction of heme oxygenase. 866 Mar 58

Changes in gene expression in the brain in response to adverse conditions, such as ischemia or excitotoxin exposure, may be part of the injury process or represent an adaptive response which may be protective during subsequent stressful events. In this review we have considered the regulation, functions and potential relationships to the pathophysiology of ischemia of several major groups of stress-induced genes, including those of the M(r) 27,000, 32,000 (heme oxygenase), 70,000 and 90,000 heat shock protein families, the glucose-regulated proteins, glucose transporters and ubiquitin. Patterns of gene expression in several injury models, including focal and global ischemia, excitotoxin/ seizure-related injury and hyperthermia are reviewed. In vitro expression studies and the phenomenon of ischemic tolerance are also discussed. It is concluded that stress gene expression provides a useful marker of cellular injury, and that disjunction of mRNA and protein expression may be indicative of imminent death in cells which survive the initial insult. Though other stress proteins may play a role, it seems unlikely that neuronal hsp70 expression is a major contributor to ischemic tolerance.
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PMID:The stress gene response in brain. 872 84

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

To examine the intracellular signaling mechanism of NO in ischemic myocardium, isolated working rat hearts were made ischemic for 30 min followed by 30 min of reperfusion. A separate group of hearts were pre-perfused with 3 mM L-arginine in the presence or absence of 650 microM of protoporphyrin, a heme oxygenase inhibitor for 10 min prior to ischemia. The release of NO was monitored using an on-line amperometric sensor placed into the right atrium. The aortic flow and developed pressure were examined to determine the effects of L-arginine on ischemic/reperfusion injury. Induction for the expression of heme oxygenase was studied by Northern hybridization. For signal transduction experiments, sarcolemmal membranes were radiolabeled by perfusing the isolated hearts with [3H] myoinositol and [14C] arachidonic acid. Biopsies were processed to determine the isotopic incorporation into various phosphoinositols as well as phosphatidic acid and diacylglycerol. cGMP was assayed by radioimmunoassay and SOD content was determined by enzymatic analysis. The release of NO was diminished following ischemia and reperfusion and was augmented by L-arginine. L-arginine reduced ischemic/reperfusion injury as evidenced by the enhanced myocardial functional recovery. Protoporphyrin modulated the effects of L-arginine. cGMP, which was remained unaffected by ischemia and reperfusion, was stimulated significantly after L-arginine treatment. The NO-mediated augmentation of cGMP was reduced by protoporphyrin suggesting that part of the effects may be mediated by CO generated through the heme oxygenase pathway. Reperfusion of ischemic myocardium resulted in significant accumulation of radiolabeled inositol phosphate, inositol bisphosphate, and inositol triphosphate. Isotopic incorporation of [3H] inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly during reperfusion. Reperfusion of the ischemic heart prelabeled with [14C] arachidonic acid resulted in modest increases in [14C] diacylglycerol and [14C] phosphatidic acid. Pretreatment of the heart with L-arginine significantly reversed this enhanced phosphodiesteratic breakdown during ischemia and early reperfusion. However, at the end of the reperfusion the inhibitory effect of L-arginine on the phosphodiesterases seems to be reduced. In L-arginine treated hearts, SOD activity was progressively decreased with the duration of reperfusion time. The results suggests for the first time that NO plays a significant role in transmembrane signaling in the ischemic myocardium. This signaling appears to be on- and off- nature, and linked with SOD content of the tissue. The signaling is transmitted via cGMP and opposes the effects of phosphodiesterases by inhibiting the ischemia/reperfusion-induced phosphodiesteratic breakdown. Our results also suggest that NO activates heme oxygenase which further stimulates the production of cGMP presumably by CO signaling. Thus, NO not only potentiates cGMP mediated intracellular signaling, it also functions as a retrograde messenger for CO signaling in heart.
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PMID:Nitric oxide--a retrograde messenger for carbon monoxide signaling in ischemic heart. 873 31

We investigated the role of carbon monoxide as a neural modulator of extracellular glutamate concentration in rat hippocampus CA1 in transient forebrain ischemia by using metalloporphyrins, which block the production of carbon monoxide through the inhibition of heme oxygenase (HO) activity. Infusion of 10 and 100 microM zinc protoporphyrin IX, which inhibits nitric oxide synthase activity as well as HO activity, significantly increased glutamate concentration compared with that on the vehicle-treated side. However, infusion of 100 microM tin mesoporphyrin IX, which inhibits only HO activity, did not affect glutamate concentration in ischemia. Our results therefore do not support the hypothesis that carbon monoxide acts as a neural messenger through the modulation of extracellular glutamate concentration in ischemia.
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PMID:Carbon monoxide, a novel neural messenger, does not modulate extracellular glutamate concentration in forebrain ischemia. 878 53

Two heme oxygenase (HO) proteins have been identified to date; HO-1, a stress-induced protein, and HO-2, a constitutively expressed isoform. Recently, it was demonstrated that HO-1 mRNA expression is increased following transient global ischemia. The present study examined the effects of global and focal ischemia on HO-1 and HO-2 protein, using immunocytochemistry. Following 20 min of ischemia (rat 4 vessel occlusion model with hypotension) and 6 h of recirculation, increased HO-1 immunoreactivity was evident in hippocampal neurons. After 24 h of recirculation, HO-1 was observed in both hippocampal neurons and astroglial cells. By 72 h, expression was primarily glial and restricted to CA1 and CA3c. In addition to hippocampus, HO-1 was also evident in both neurons and glia in cerebral cortex and thalamus, and in striatal glial cells. Twenty-four hours following permanent focal ischemia, HO-1 immunoreactivity was observed in astroglial cells in the penumbra region surrounding the infarct. In contrast to HO-1, the pattern of HO-2 immunoreactivity was not altered following transient global or permanent focal ischemia. The increased expression of HO-1 following ischemia may confer protection against oxidative stress, but might also contribute to the subsequent neuronal degeneration.
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PMID:Permanent focal and transient global cerebral ischemia increase glial and neuronal expression of heme oxygenase-1, but not heme oxygenase-2, protein in rat brain. 880 31


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