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

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

Gaseous monoxides such as nitric oxide (NO) and carbon monoxide (CO) have recently attracted great interest as a regulator of cell and organ functions. When exposed to endotoxin, cytokines or ischemia-reperfusion, the liver produces larger amounts of NO than those in the control via the activity of inducible NO synthase which can alter a variety of organ functions such as sensitivity of vascular tone to catecholamine, mitochondrial membrane potential, biliary transport and tissue regeneration. On the other hand, the liver constitutively produces CO through the reaction of heme oxygenase. CO generated in the liver tissue can reach sinusoidal vessels and relax fat-storing Ito cells--the liver-specific microvascular pericytes covering the sinusoidal wall--and thereby serves as an endogenous modulator of vascular tone. Two isoforms of the CO-generating enzyme have been characterized: heme oxygenase-1 which is inducible by a variety of stressors, and heme oxygenase-2 which constitutes the major enzyme activity under physiological conditions in the liver. Although it is still unknown whether excessive CO generation by the inducible heme oxygenase activity may preserve or jeopardize the integrity of microvascular function in the liver, the potential importance of this double-edged molecule has just emerged much like nitric oxide, another gaseous molecule that was established as a neurovascular mediator inducing vascular cell relaxation. This article provides an overview of the pathophysiological roles of these gaseous monoxides in regulation of microvascular function in the liver.
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PMID:Gaseous monoxides: a new class of microvascular regulator in the liver. 891 86

Selenium induces several proteins, including glutathione and stress proteins. These proteins have been shown to be cardioprotective against oxidative injury. To determine whether ebselen, a seleno-organic compound, can also induce these proteins and exert cardioprotective action, we examined the effects of preconditioning with ebselen on glutathione metabolism and stress protein expression and on myocyte injury induced by oxidative stress. Treatment of cultured cardiac myocytes with ebselen (0.3-30 microM) for 24 hr increased the reduced glutathione content. Glutathione reductase activity, but not glutathione peroxidase activity, was significantly elevated in a dose-dependent manner. Pretreatment with ebselen increased the expression of such stress proteins as heat shock protein 70 and heme oxygenase-1 (heat shock protein 32) in cardiac myocytes, as assessed by Western blotting. Expression of heat shock protein 70 was increased only at a higher dose of ebselen (30 microM), whereas expression of heme oxygenase-1 was markedly increased at a lower dose of ebselen (3 microM). Under these conditions, the myocyte injury induced by hydrogen peroxide or simulated ischemia/reperfusion, assessed by the release of lactate dehydrogenase into the culture medium, was reduced by ebselen pretreatment in a dose-dependent manner. Results indicated that cardiac myocytes pharmacologically preconditioned with ebselen for 24 hr exhibited resistance to oxidative injury, possibly via the up-regulation of glutathione metabolism and the expression of stress proteins.
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PMID:Effects of preconditioning with ebselen on glutathione metabolism and stress protein expression. 919 Aug 85

Although there is substantial evidence suggesting that the integrity of the microcirculation is an important determinant of tissue viability during reperfusion after ischemia in the liver, as well as other tissues, the mechanisms responsible for microvascular failure are not fully understood. It is now recognized that the microvascular response to reperfusion, similar to the whole organism response to shock, can consist of either a rapid exacerbation of injury after a severe ischemic episode or, alternatively, a more slowly developing alteration in responsiveness that occurs after a less severe insult. In the more slowly developing response, the alterations in vascular status are the result of up-regulation of stress-induced vascular mediators such as endothelin, nitric oxide synthase (NOS), and heme oxygenase, as well as changes in the reactivity of the effector cells to the mediators. The mechanisms for change in reactivity of vascular cells range from changes in receptor expression to overt phenotypic transformation, as can occur in the hepatic stellate cells in response to repeated injury. When maintained in balance, these counteracting constrictor and dilator influences can be protective; however, local imbalance can result in focal ischemia, thus propagating the injury. Thus, the remodeling of the hepatic microvascular responsiveness during reperfusion after ischemia may serve as a useful paradigm for consideration of the overall response of the organism to shock.
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PMID:Remodeling of hepatic microvascular responsiveness after ischemia/reperfusion. 926 96

Evidence has been presented that disturbances of endoplasmic reticulum (ER) calcium homeostasis contribute to neuronal injury induced by transient cerebral ischemia. The present series of experiments was designed to study whether the expression of heme oxygenase-1 (HO-1), which is markedly increased after transient cerebral ischemia, is also activated by a disturbance of ER calcium homeostasis. ER calcium pools were depleted by a 30 min exposure of primary cortical and hippocampal neurons to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase. In cortical neurons, HO-1 mRNA levels (analysed by quantitative polymerase chain reaction (PCR)) were significantly increased (22-fold) 12 h after exposure to Tg but had decreased again to only nine times control levels by 24 h after treatment. In hippocampal neurons, a significant increase in HO-1 mRNA levels was already apparent 4 h after treatment (8.3-fold over controls), levels rose further to 27-fold over controls after 6 h, and stayed high for up to 24 h after treatment (34-fold over controls). The similarity between the pattern of changes in HO-1 mRNA levels induced by transient ischemia and depletion of ER calcium stores suggests common underlying mechanisms.
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PMID:Activation of heme oxygenase-1 expression by disturbance of endoplasmic reticulum calcium homeostasis in rat neuronal cell culture. 929 Nov 44

Total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min hepatic ischemia, we examined a time course of the changes in the steady-state levels of heme oxygenase-1 (HO-1) mRNA and protein in the livers. The levels of HO-1 mRNA was transiently induced and peaked at 4 h after the start of reperfusion. In addition, a pattern of the time course of HO-1 protein levels was similar to that of HO-1 mRNA levels. Immunohistochemical analysis clearly showed that the localization of HO-1 protein induced by hepatic ischemia was restricted to the hepatocytes in the pericentral vein.
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PMID:Immunohistochemical analysis of heme oxygenase-I in rat liver after ischemia. 935 73

The heme oxygenase-1 gene, HO-1, induced by heme, ischemia, and heat shock, metabolizes heme to biliverdin, free iron, and carbon monoxide. Though the distribution of HO-1 has been described in normal rat brain, little is known about how extracellular heme proteins in the subarachnoid space distribute in brain. To address this issue, hemoglobin was injected into the cisterna magna of adult rats. Expression of HO-1 in these animals was compared with saline-injected, BSA-injected, and uninjected controls. Western blot analysis showed that 24 hours after injection oxyhemoglobin increased HO-1 levels approximately four- to fivefold in all brain regions studied compared with saline-injected and BSA-injected controls. In the brain, HO-1 immunoreactivity was evident at 4 hours and peaked at 24 hours after oxyhemoglobin injections, returning to control levels by 4 to 8 days. This HO-1 induction was detected mainly in cells with small, rounded somas bearing two to four truncated processes, a morphology consistent with that of microglia. These cells were double-stained with the microglial marker, OX42, in every brain region examined. It is proposed that subarachnoid hemoglobin may be taken up into microglia wherein heme induces HO-1.
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PMID:Heme oxygenase-1 is induced in glia throughout brain by subarachnoid hemoglobin. 949 42

To clarify whether heme oxygenase-1 (HO-1) protein plays a protective role against cerebral ischemia, we investigated the effects of an HO inhibitor (tin mesoporphyrin IX [SnMP] three doses of 30 micromol/kg, intraperitoneally) and an HO inducer (hemin, three doses of 30 micromol/kg, intraperitoneally) on the pathologic outcome and on the immunohistochemical reaction for HO-1 after 20-minute transient forebrain ischemia followed by 3-day reperfusion in rats. Hemin significantly increased viable neurons in the cortex (compared to the SnMP-treated group, P < .05) and striatum (compared to the saline-treated group at P < .01 and SnMP-treated group at P < .05), and intense HO-1 immunoreactivity was observed in cortex and striatum, whereas the administration of SnMP tended to decrease viable neurons in the parietal cortex. In contrast, neither hemin nor SnMP affected the pathologic outcome in the CA1 and CA3 hippocampi, in which HO-1 immunoreactivity was weak. These results suggest that induction of HO-1 protein may contribute to cellular defense against ischemic damage in brain regions where potential ability to synthesize HO-1 is retained in ischemia.
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PMID:Induction of heme oxygenase protein protects neurons in cortex and striatum, but not in hippocampus, against transient forebrain ischemia. 959 48

Recent studies strongly suggest that oxidative stresses participate in ischemia/reperfusion-induced neurodegeneration. In addition, heme oxygenase (HO) and major histocompatibility complex (MHC) antigens serve as functional molecules against oxidative stress and as self-recognition markers in the immune system, respectively. In this study, we examined the induction of HO and MHC antigens in the rat hippocampus after transient forebrain ischemia. The protein level of HO-1 was significantly enhanced after an episode of ischemia. After ischemia, HO-1 expression was observed early but transiently in the CA1 pyramidal neurons and later but continuously in glial cells. Glial cells expressing HO-1 were predominantly ameboid microglia, but not astrocytes. Ameboid microglia expressing HO-1 were predominantly localized with MHC class II antigens. These results indicate that (1) HO-1 expression in CA1 pyramidal neurons may be harmful, and (2) ischemia induces HO-1 in ameboid microglia that express MHC class II antigens, indicating a very specific microglial stress protein response.
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PMID:Induction of heme oxygenase-1 and major histocompatibility complex antigens in transient forebrain ischemia. 970 43

Maintenance of hepatic microcirculatory flow after ischemia of the liver is essential to prevent hepatic dysfunction. Thus, we determined the differential role of carbon monoxide (CO) and nitric oxide (NO) in the intrinsic control of sinusoidal perfusion, mitochondrial redox state, and bile production in the isolated perfused rat liver after hemorrhagic shock. Administration of tin protoporphyrin-IX (50 microM), a specific inhibitor of the CO generating enzyme heme oxygenase, caused a decrease in sinusoidal flow that was more pronounced after shock compared with sham shock, as determined by in situ epifluorescence microscopy. This was associated with a shift in hepatocellular redox potential to a more reduced state (increased fluorescence intensity of reduced pyridine nucleotides in hepatocytes, decreased acetoacetate/beta-hydroxybutyrate ratio in the perfusate) and a profound reduction in bile flow. In sharp contrast, the preferential inhibitor of the inducible isoform of NO synthase S-methylisothiourea sulfate (100 microM) did not affect sinusoidal flow, hepatic redox state, or function. This indicates that 1.) endogenously generated CO preserves sinusoidal perfusion after hemorrhagic shock, 2.) protection of the hepatic microcirculation by CO may serve to limit shock-induced liver dysfunction, and 3.) in contrast to CO, inducible NO synthase-derived NO is of only minor importance for the intrinsic control of hepatic perfusion and function under these conditions.
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PMID:Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. 973 56


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