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)

Ischemia-reperfusion (IR) injury is an intractable process associated not only with therapeutic recanalization of vessels, but also with partial resection or transplantation of solid organs including liver. To develop methods for predicting the degree of hepatic IR injury and further to identify injured cells, we studied the formation of 8-hydroxy-2'-deoxy-guanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE)-modified proteins in the normothermic hepatic IR model of rats using immunohistochemistry, high-performance liquid chromatography (HPLC) determination and Western blot. The Pringle maneuver for either 15 or 30 min duration produced reversible or lethal damage, respectively. The levels of both products were significantly increased in proportion to ischemia duration 40 min after reperfusion, suggesting the involvement of hydroxyl radicals. Increased immunoreactivity of 8-OHdG was observed not only in the nuclei of hepatocytes but also in those of bile canalicular and endothelial cells. However, immunoreactivity of HNE-modified proteins was detected in the cytoplasm of hepatocytes, which was confirmed by Western blot, and in addition, in the nuclei of hepatocytes after severe injury. Thus, localization of the two oxidatively modified products was not identical. Our data suggest that these two products could be used for the assessment of hepatic IR injury in tissue, but that the biological significance of the two products might be different.
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PMID:Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in rat liver after ischemia-reperfusion: distinct localization of the two oxidatively modified products. 1123 93

Delayed neuronal death in the CA1 of the hippocampus following global ischemia has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and the generate reactive oxygen species in the neurons. In the present study, we investigated whether oxidative DNA damages may be correlated with NR subunits (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased. These results suggest that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger neuronal damages at early time after ischemia, and free radical damage including oxidative DNA damage may eventually promote the delayed neuronal death in this region.
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PMID:The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemia-reperfusion insult. 1124 42

EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt, is a novel antioxidant. In this study, we investigated a reduction of oxidative neuronal cell damage with EPC-K1 by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat brain with 60 min transient middle cerebral artery occlusion, in association with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and staining for total and active caspase-3. Treatment with EPC-K1 (20 mg kg(-1) i.v.) significantly reduced infarct size (p < 0.05) at 24 h of reperfusion. There were no positive cells for 8-OHdG and TUNEL in sham-operated brain, but numerous cells became positive for 8-OHdG, TUNEL and caspase-3 in the brains with ischemia. The number was markedly reduced in the EPC-K1 treated group. These reductions were particularly evident in the border zone of the infarct area, but the degree of reduction was less in caspase-3 staining than in 8-OHdG and TUNEL stainings. These results indicate EPC-K1 attenuates oxidative neuronal cell damage and prevents neuronal cell death.
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PMID:Attenuation of oxidative DNA damage with a novel antioxidant EPC-K1 in rat brain neuronal cells after transient middle cerebral artery occlusion. 1154 42

Ischemia/reperfusion is known to result in DNA fragmentation and cell death in kidney tubular epithelium, but the endonucleases responsible for this DNA damage have not been identified. DNA substrate gel analysis of extracts from normal rat kidney cortex revealed the presence of a DNase with an apparent molecular mass of 30 to 34 kD. This enzyme is not a dimer of the previously described nuclear 15-kD endonuclease in kidney cells. Partially purified DNase exhibited characteristics similar to those of rat DNase I. The DNase was able to digest circular DNA (endonuclease), required both Ca(2+) and Mg(2+) ions, and was inhibited by Zn(2+) and by aurintricarboxylic acid; it was not inhibited by G-actin. Rat kidneys were subjected to 40 min of ischemia, followed by 0, 1, 4, 16, or 48 h of reperfusion. The activity of the DNase in cytosolic and nuclear extracts, the 200-bp ladder-generating activity, and 3'OH strand breaks in nuclear DNA were simultaneously increased after ischemia, during the first hours of reperfusion. Oxidative DNA damage, measured as 8-hydroxydeoxyguanosine content, did not coincide with endonuclease-generated DNA breaks. Oxidative DNA damage was increased during ischemia and gradually decreased during reperfusion. Phosphorothioated DNase I antisense oligodeoxynucleotide introduced into cultured NRK-52E rat kidney epithelial cells inhibited DNA fragmentation and attenuated cell death induced by hypoxia/reoxygenation in vitro. The data indicate that the DNase I-like endonuclease may contribute to DNA fragmentation in reperfused rat kidneys.
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PMID:DNase I-like endonuclease in rat kidney cortex that is activated during ischemia/reperfusion injury. 1191 59

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

Although oxidative stress and excitotoxicity may be interdependent mechanisms that are involved in delayed neuronal death, the temporal participation of these events in the early stage after ischemia-reperfusion insult is unclear. Therefore, in the present study, using the gerbil global ischemic model we investigated whether oxidative stress could be correlated with the expression of the glutamate transporters in the hippocampus, and whether these events are related and cooperate in the events that link ischemia to neuronal death in vivo. Thirty minutes after ischemia, the intensities of glutamate transporter-1 (GLT-1), glutamate/aspar-tate transporter (GLAST), and 8-hydroxy2'-deoxy-guanosine (8-OHdG) immunoreactivities were markedly increased in the hippocampal CA1 area. In contrast, excitatory amino acid carrier-1 (EAAC-1) immunoreactivity was 30% lower in the CA1 area than in the sham level. At 3 h post-reperfusion, the EAAC-1 expression began to increase in the CA1 area. Twelve hours after reperfusion, the reduction of both GLT-1 and GLAST immunoreactivity was salient, while the EAAC-1 immunoreactivity level intensified significantly. The 8-OHdG immunoreactivity peaked at this time point. These findings suggest that oxidative stress and alterations in the glutamate transporter expression in the CA1 area may simultaneously trigger neuronal damages very early after ischemia.
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PMID:Oxidative DNA damage and alteration of glutamate transporter expressions in the hippocampal Ca1 area immediately after ischemic insult. 1213 89

The 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a DNA base modified by reactive oxygen species (NOS). The 8-OHdG has been shown to be generated in the brain during ischemia-reperfusion. We performed the immunohistochemical study of 8-OHdG in the brains of autopsied specimens. Age had a statistically significantly negative correlation with 8-OHdG immunoreactivity in glial cells. The 8-OHdG immunoreactivity in glial cells was not increased in the surrounding border of the infarction compared with the non-ischemic areas in the same cases. There was no statistically significant difference in the disease-free areas between infarction and the age-matched control cases. This indicates that 8-OHdG immunoreactivity may not be a sensitive tool to evaluate the infarction injury in human autopsied specimens.
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PMID:Age-associated decrease in 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity in the autopsied brain. 1293 88

Atrial fibrillation (AF) is the most common cause of arrhythmia and is an aging-related disease encountered in clinical practice. The electrophysiological remolding with Ca(2+) overloading and cellular structure changes were found in cardiomyocytes of AF patients. In previous studies, increased oxidative stress and oxidative damage was found in cardiomyocytes during the ischemia/reperfusion injury. Besides, mitochondrial DNA (mtDNA) deletion and mtDNA proliferation occur frequently in affected tissues of patients with certain degenerative diseases and during aging of the human. However, it remains unclear whether high oxidative stress and alteration of mtDNA play a role in the pathophysiology of AF. In this study, we first screened for large-scale deletions of mtDNA in the atrial muscle of AF patients by long-range polymerase chain reaction (PCR). The results showed that large-scale deletions between nucleotide positions 7900 and 16500 of mtDNA occurred at a high frequency. Among them, the 4977 bp deletion was the most frequent and abundant one, and the mean proportion of mtDNA with the 4977 bp deletion in the atrial muscle of the patients with AF was 3.75-fold higher than that of the patients without AF (p <.005). Furthermore, quantitative PCR was performed to evaluate lesions in mtDNA caused by oxidative damage. We found that the degree of mtDNA damage in the patients with AF was greater than that of the patients without AF (3.29 vs.1.60 per 10 kb, p <.0005). The 8-OHdG, which is one of the most common products of oxidative damage to DNA, was also found at a higher frequency in mtDNA of patients with AF as compared with those without AF. In addition, the mtDNA content was found to increase significantly in the patients with AF (p =.0051). The level of mtDNA lesion and the mtDNA content was positively correlated (r = 0.44). These results suggest that oxidative injury and deletion of mtDNA in cardiac muscle are increased in the patients with AF, which may contribute to the impairment of bioenergetic function of mitochondria and induction of the oxidative vicious cycle involved in the pathogenesis of atrial myopathy in AF.
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PMID:Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation. 1460 30

Grape seed extract (GSE) possess cardioprotective abilities by functioning as in vivo antioxidants and by virtue of their ability to directly scavenge ROS including hydroxyl and peroxyl radicals. In the present study, we investigated the neuroprotective effects of grape seed extract (GSE) in the gerbil hippocampus after 5 min transient forebrain ischemia. Neuronal cell density in GSE-treated ischemic animals was significantly increased as compared with vehicle-treated ischemic animals 4 days after ischemic insult. In the GSE-treated groups, about 60% of pyramidal cells of the sham-operated group were stained with cresyl violet 4 days after ischemic insult. In this study, we found that GSE had neuroprotective effects on neuronal injury by inhibiting DNA damage in the CA1 region after ischemia. In vehicle-treated groups, 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity was significantly changed time-dependently, whereas the immunoreactivity in the GSE-treated group was similar to the sham-operated group. In addition, we confirmed that astrocytes and microglia did not show significant activation in the CA1 region 4 days after ischemia-reperfusion, because many CA1 pyramidal cells were not damaged. Therefore, these results suggest that GSE can protect ischemic neuronal damage by inhibiting DNA damage after transient forebrain ischemia.
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PMID:Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia. 1530 66

Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.
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PMID:Peripheral oxidative biomarkers constitute a valuable indicator of the severity of oxidative brain damage in acute cerebral infarction. 1546 43


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