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)

Heat shock preconditioning (HSPC) is a promising strategy for providing ischemic tolerance. The objective of this study is to investigate the effectiveness of HSPC in preventing oxidative damage of cellular proteins and DNA during ischemia-reperfusion of the liver. Male Wistar rats were divided into a heat shock group (group HS) and control (group C). Forty-eight hours prior to ischemia, rats in group HS received HSPC at 42 degrees C for 15 min. All rats received hepatic warm ischemia for 30min and subsequent reperfusion. The formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) modified proteins in liver tissue, survival rate of the animals, and changes in biochemical and histological parameters were compared between groups. Heat shock protein 72 was produced only in group HS. The 7-day survival of rats was significantly better in group HS (10/10) than in group C (5/10) (p < 0.01). The serum release of alanine aminotransferase (n = 10, p < 0.01) and the concentration of adenosine triphosphate in liver tissue (n = 10, p < 0.01) 40min after reperfusion was significantly better in group HS than in group C. The formation of 8-OHdG in liver tissue measured by high-performance liquid chromatography was suppressed in group HS (p < 0.01). The production of HNE-modified proteins as determined by Western-blot analysis was also decreased in group HS. These results were also confirmed by immunohistochemical analysis. As determined by levels of 8-OHdG and HNE-modified proteins produced during ischemia-reperfusion of the liver, HSPC reduced the oxidative injury of cellular proteins and DNA in the liver tissue.
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PMID:Heat shock preconditioning reduces the formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal modified proteins in ischemia-reperfused liver of rats. 1199 85

Prolonged hepatic warm ischemia has been incriminated in oxidative stress after reperfusion. However, the magnitude of oxidative stress during ischemia has been controversial. The aims of the present study were to elucidate whether lipid peroxidation progressed during ischemia and to clarify whether oxidative stress during ischemia aggravated the oxidative damage after reperfusion. Rats were subjected to 30 to 120 min of 70% warm ischemia alone or followed by reperfusion for 60 min. Lipid peroxidation (LPO) was evaluated by amounts of phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH) as primary LPO products. Total amounts of malondialdehyde and 4-hydroxy-2-nonenal (MDA + 4-HNE), degraded from hydroperoxides, were also determined. PC-OOH and PE-OOH significantly increased at 60 and 120 min ischemia with concomitant increase of oxidized glutathione. These hydroperoxides did not increase at 60 min reperfusion after 60 min ischemia, whereas they did increase at 60 min reperfusion after 120 min ischemia with deactivation of phospholipid hydroperoxide glutathione peroxidase and superoxide dismutase. The amount of MDA + 4-HNE exhibited similar changes, but the velocity of production dropped with ischemic time longer than 60 min. In conclusion, oxidative stress progressed during ischemia and triggered the oxidative injury after reperfusion. Secondary LPO products are less sensitive, especially during ischemia, which may cause possible underestimation and discrepancy.
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PMID:Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and reperfusion of rat liver. 1585 55

Remodeling of myocardial cell membranes is a major feature of advanced age. Mitochondrial function, crucial to sustaining energy production and management of myocardial metabolism, is impacted by age-dependent remodeling and ultimately exhibits a diminished threshold for excess Ca(2+) buffering during events that stimulate increased myocardial Ca(2+), such as augmented cardiac work, oxidative stress or post-ischemic reflow. Relative Ca(2+) intolerance, augmented superoxide formation and reduced efficiency in the management of reactive oxygen species, are important mitochondrial factors (of many) that are apparent in senescence and predispose the myocardium to be more vulnerable to ischemic injury. In addition to cell death, surviving myocytes increase in size and exhibit altered gene expression of key effector proteins, including those that sustain Ca(2+) homeostasis. Age-associated mitochondrial membrane changes include increases in membrane rigidity, cholesterol, phosphatidylcholine, omega-6 polyunsaturated fatty acids (PUFA), 4-hydroxy-2-nonenal, and decreases in omega-3 PUFA and cardiolipin. These effects have been shown in animal studies to be exaggerated by diet rich in long chain omega-6 PUFA (i.e., arachidonic acid), and have profound consequences on the efficacy of membrane proteins involved with ion homeostasis, signal transduction, redox reactions and oxidative phosphorylation. However, some of the age-related detrimental adaptations may be beneficially modified by dietary strategy. Diet rich in omega-3 PUFA reverses the age-associated membrane omega-3:omega-6 PUFA imbalance, and dysfunctional Ca(2+) metabolism, facilitating increased efficiency of mitochondrial energy production and improved tolerance of ischemia and reperfusion.
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PMID:Effect of dietary polyunsaturated fatty acids on age-related changes in cardiac mitochondrial membranes. 1591 88

Both in vivo models of ischemia/reperfusion and in vitro models of hypoxia (H)/reoxygenation (R) have demonstrated the crucial role of the Rac1-regulated NADPH oxidase in the production of injurious reactive oxygen species (ROS) by vascular endothelial cells (ECs). Since membrane lipid peroxidation has been established as one of the mechanisms leading to cell death, we examined lipid peroxidation in H/R-exposed cultured human umbilical vein ECs (HUVECs) and the role of Rac1 in this process. H (24 h at 1% O2)/R (5 min) caused an increase in intracellular ROS production compared to a normoxic control, as measured by dichlorofluorescin fluorescence. Nutrient deprivation (ND; 24 h), a component of H, was sufficient to induce a similar increase in ROS under normoxia. Either H(24 h)/R (2 h) or ND (24 h) induced increases in lipid peroxidation of similar magnitude as measured by flow cytometry of diphenyl-1-pyrenylphosphine-loaded HUVECs and Western blotting analysis of 4-hydroxy-2-nonenal-modified proteins in cell lysates. In cells infected with a control adenovirus, H (24 h)/R (2 h) and ND (24 h) resulted in increases in NADPH-dependent superoxide production by 5- and 9-fold, respectively, as measured by lucigenin chemiluminescence. Infection of HUVECs with an adenovirus that encodes the dominant-negative allele of Rac1 (Rac1N17) abolished these increases. Rac1N17 expression also suppressed the H/R- and ND-induced increases in lipid peroxidation. In conclusion, ROS generated via the Rac1-dependent pathway are major contributors to the H/R-induced lipid peroxidation in HUVECs, and ND is able to induce Rac1-dependent ROS production and lipid peroxidation of at least the same magnitude as H/R.
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PMID:Rac1 inhibition protects against hypoxia/reoxygenation-induced lipid peroxidation in human vascular endothelial cells. 1609 26

Remodeling of myocardial cell membranes is a major feature of advanced age. Mitochondrial function, crucial to sustaining energy production and management of myocardial metabolism, is impacted by age-dependent remodeling and ultimately exhibits a diminished threshold for excess Ca2+ buffering during events that stimulate increased myocardial Ca2+, such as augmented cardiac work, oxidative stress or post-ischemic reflow. Relative Ca2+, intolerance, augmented superoxide formation and reduced efficiency in the management of reactive oxygen species, are important mitochondrial factors (of many) that are apparent in senescence and predispose the myocardium to be more vulnerable to ischemic injury. In addition to cell death, surviving myocytes increase in size and exhibit altered gene expression of key effector proteins, including those that sustain Ca2+ homeostasis. Age-associated mitochondrial membrane changes include increases in membrane rigidity, cholesterol, phosphatidylcholine, omega-6 polyunsaturated fatty acids (PUFA), 4-hydroxy-2-nonenal, and decreases in omega-3 PUFA and cardiolipin. These effects have been shown in animal studies to be exaggerated by diet rich in long chain omega-6 PUFA (i.e. arachidonic acid), and have profound consequences on the efficacy of membrane proteins involved with ion homeostasis, signal transduction, redox reactions and oxidative phosphorylation. However, some of the age-related detrimental adaptations may be beneficially modified by dietary strategy. Diet rich in omega-3 PUFA reverses the age-associated membrane omega-3:omega-6 PUFA imbalance, and dysfunctional Ca2+ metabolism, facilitating increased efficiency of mitochondrial energy production and improved tolerance of ischemia and reperfusion.
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PMID:Effect of dietary polyunsaturated fatty acids on age-related changes in cardiac mitochondrial membranes. 1625 72

The proteasome represents a major intracellular proteolytic system responsible for the degradation of oxidized and ubiquitinated proteins in both the nucleus and cytoplasm. We have previously reported that proteasome undergoes modification by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) and exhibits declines in peptidase activities during cardiac ischemia/reperfusion. This study was undertaken to characterize the effects of HNE on the structure and function of the 20S proteasome. To assess potential tissue-specific differences in the response to HNE, we utilized purified 20S proteasome from heart and liver, tissues that express different proteasome subtypes. Following incubation of heart and liver 20S proteasome with HNE, changes in the 2D gel electrophoresis patterns and peptidase activities of the proteasome were evaluated. Proteasome subunits were identified by mass spectrometry prior to and following treatment with HNE. Our results demonstrate that specific subunits of the 20S proteasome are targeted for modification by HNE and that modified proteasome exhibits selective alterations in peptidase activities. The results provide evidence for a likely mechanism of proteasome inactivation in response to oxidative stress particularly during cardiac ischemia/reperfusion.
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PMID:Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes. 1653 Jul 22

Increased production of reactive oxygen species (ROS) following cerebral ischemia-reperfusion (I/R) is an important underlying cause for neuronal injury leading to delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase inhibitor can protect against ischemia-induced ROS generation and decrease DND. Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30 min prior to ischemia significantly attenuated the early increase in HNE in hippocampus measured at 3 h after I/R. Apocynin also protected against I/R-induced neuronal degeneration and DND, oxidative DNA damage, and glial cell activation. Taken together, the neuroprotective effects of apocynin against ROS production during early phase of I/R and subsequent I/R-induced neuronal damage provide strong evidence that inhibition of NADPH oxidase could be a promising therapeutic mechanism to protect against stroke damage in the brain.
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PMID:Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus. 1665 Aug 38

Schwannomas, particularly of vestibular origin, often accompany degenerative hypocellular areas known as Antoni B patterns; however, the detailed mechanism is uncertain. Eosinophilic hyaline droplets (EHD), the substantial nature of which are autophagic vacuoles, preferentially appear in acoustic schwannomas and distribute around areas of Antoni B. We investigated their common background using schwannomas with (15 cases) or without (10 cases) EHD, and demonstrated that EHD showed selective immunoreactivity with an anti-nitrotyrosine antibody, suggesting the overproduction of nitric oxide in this condition. The expression of inducible nitric oxide synthase was emphasized in infiltrating macrophages around hyalinized vessels. Protein-bound 4-hydroxy 2-nonenal, another oxidative stress marker, was detected in Antoni B tissue, but not in EHD. Antibodies to cleaved caspase-3 and single strand DNA, indicators of apoptosis, did not label tumors cells in Antoni B areas as well as EHD-bearing cells. The morphology and the mitotically static state of EHD-laden cells are phenotypically similar to autophagic cell death; however, autophagy in normal cells is a cell survival strategy against starvation, so the possibility remains that EHD are formed in that context. In either case, schwannomas may show a characteristic autophagic change by an endogenous mechanism. Tumor growth in a narrow intracranial space and resultant ischemia by self-oppression were postulated to be an initial event, because ischemia-reperfusion injury is a major source of reactive oxygen species and ischemia is also a potent trigger of autophagy as well as of tissue degeneration. Moreover, potential roles of chemokines and hemosiderosis are discussed.
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PMID:Oxidative stress is related to the formation of Antoni B patterns and eosinophilic hyaline droplets in schwannomas. 1764 38

Transient global brain ischemia induced by cardiac arrest and resuscitation (CAR) results in reperfusion injury associated with oxidative stress. Oxidative stress is known to produce delayed selective neuronal cell loss and impairment of brainstem function, leading to post-resuscitation mortality. Levels of 4-hydroxy-2-nonenal (HNE) modified protein adducts, a marker of oxidative stress, was found to be elevated after CAR in rat brain. In this study we investigated the effects of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) on the recovery following CAR in the aged rat brain. Male Fischer 344 rats (6, 12 and 24-month old) underwent 7-minute cardiac arrest before resuscitation. Brainstem function was assessed by hypoxic ventilatory response (HVR) and HNE-adducts were measured by western blot analysis. Our data showed that in the 24-month old rats, overall survival rate, hippocampal CAl neuronal counts and HVR were significantly reduced compared to the younger rats. With PBN treatment, the recovery was improved in the aged rat brain, which was consistent with reduced HNE adducts in brain following CAR. Our data suggest that aged rats are more vulnerable to oxidative stress insult and treatment with PBN improves the outcome following reperfusion injury. The mechanism of action is most likely through the scavenging of reactive oxygen species resulting in reduced lipid peroxidation.
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PMID:Increased sensitivity to transient global ischemia in aging rat brain. 1772 65

Ethanol preconditioning (EtOH-PC) refers to a phenomenon in which tissues are protected from the deleterious effects of ischemia/reperfusion (I/R) by prior ingestion of ethanol at low to moderate levels. In this study, we tested whether prior (24 h) administration of ethanol as a single bolus that produced a peak plasma concentration of 42-46 mg/dl in gerbils would offer protective effects against neuronal damage due to cerebral I/R. In addition, we also tested whether reactive oxygen species (ROS) derived from NADPH oxidase played a role as initiators of these putative protective effects. Groups of gerbils were administered either ethanol or the same volume of water by gavage 24 h before transient global cerebral ischemia induced by occlusion of both common carotid arteries for 5 min. In some experiments, apocynin, a specific inhibitor of NADPH oxidase, was administered (5 mg/kg body wt, i.p.) 10 min before ethanol administration. EtOH-PC ameliorated behavioral deficit induced by cerebral I/R and protected the brain against I/R-induced delayed neuronal death, neuronal and dendritic degeneration, oxidative DNA damage, and glial cell activation. These beneficial effects were attenuated by apocynin treatment coincident with ethanol administration. Ethanol ingestion was associated with translocation of the NADPH oxidase subunit p67(phox) from hippocampal cytosol fraction to membrane, increased NADPH oxidase activity in hippocampus within the first hour after gavage, and increased lipid peroxidation (4-hydroxy-2-nonenal) in plasma and hippocampus within the first 2 h after gavage. These effects were also inhibited by concomitant apocynin treatment. Our data are consistent with the hypothesis that antecedent ethanol ingestion at socially relevant levels induces neuroprotective effects in I/R by a mechanism that is triggered by ROS produced through NADPH oxidase. Our results further suggest the possibility that preconditioning with other pharmacological agents that induce a mild oxidative stress may have similar therapeutic value for suppressing stroke-mediated damage in brain.
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PMID:Ethanol preconditioning protects against ischemia/reperfusion-induced brain damage: role of NADPH oxidase-derived ROS. 1776 1


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