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)

Cells primed by sublethal stress transiently overproduce heat shock proteins (HSPs) and thereby develop tolerance to the next lethal stress. This response in organisms is called the stress response and involves the induction of HSPs. To assist the liver in developing tolerance for warm ischemia-reperfusion injury, which sometimes jeopardizes the patients after extended surgery for malignancies with vascular invasion in the liver, basic experiments to activate the stress response using stress preconditioning were performed. Heat shock preconditioning in rat livers has been shown to induce tolerance against warm ischemia-reperfusion injury in normal, fibrotic, and steatotic livers. Ischemic preconditioning using short-term Pringle's maneuver and pharmacological preconditioning using doxorubicin were also effective. In rats, heat shock preconditioning protected livers from free radical injury induced by the oral administration of carbon tetrachloride. The above data were supported by animal survival, suppression of serum transaminase levels, and improved energy status of the liver after intervention. Increased production of HSP72 was observed after preconditioning. In addition, the significance of HSP production as a stress parameter was demonstrated during the reperfusion of congested portal blood to the ischemic liver. The ill effect of congested portal blood could not be detected by conventional parameters but was detected by observing the increase in HSP72 production. Stress preconditioning seems to be a promising strategy to counter the damaging effect of hepatic warm ischemia during liver surgery and liver perfusion.
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PMID:Implications of heat shock proteins during liver surgery and liver perfusion. 967 Feb 77

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher (P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant (P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels (P < 0. 05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.
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PMID:Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. 979 Oct 63

1. Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. 2. The mRNAs for 72-kd (HSP72) and 73-kd (HSC73) heat shock proteins (HSPs), which are located mainly in the cytoplasm, were greatly induced together in CA1 cells, with a peak at 1-2 days in gerbils. However, immunoreactive HSP72 protein was only minimally expressed in CA1 neurons. 3. The mRNA for mitochondrial HSP60 began to increase at 3 hr in CA1 cells and was sustained until 1 day. 4. The level of mRNA for cytochrome c oxidase subunit I (COX-I) progressively decreased in CA1 neurons after a transient ischemia and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed an early decrease in CA1 cells and was followed by a reduction in the level of COX-I DNA after 2 days. 5. These results suggest that HSP gene inductions were inhibited at the translational level but that mitochondrial DNA expression was disturbed at the transcriptional level. A disturbance of mitochondrial DNA expression could cause progressive failure of energy production of CA1 cells that eventually results in neuronal cell death.
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PMID:Stress protein inductions after brain ischemia. 987 77

Genetically hypertensive animals are characterized by greater thermosensitivity and overexpression of heat shock proteins (HSP) upon thermal stimulation. We examined HSP72 expression under conditions of brief coronary occlusion or thermal stimulation, and the effects of the severity of these stimuli and of myocardial hypertrophy on the expression in hearts of spontaneously hypertensive rat (SHR) and Wistar Kyoto rat (WKY) groups, A snare was created around the left coronary artery in the SHR (n = 16) and WKY (n = 19) groups. In 7 WKY rats, the ascending aorta was banded and a snare was created simultaneously (WKY-AoB). By tying the snare, 4 weeks later, we applied 5- or 10-min coronary occlusion without opening the chest. For thermal stimulation, the SHR (n = 13) and WKY (n = 11) rats were placed in a 42 degrees C chamber for 15 or 40 min. The mRNA or protein level was estimated 1 or 24h after stimulation. In the SHR vs WKY groups, the mRNA and protein levels were higher after 5-min occlusion or 15-min thermal stimulation. After 10-min occlusion or 40-min thermal stimulation the difference was no longer observed. The overexpression was not observed in the WKY-AoB group despite the presence of hypertrophy similar to that seen in the SHR group (3.11+/-0.11 vs 3.20+/-0.06 mg/g in left ventricular weight/body weight). The HSP72 was overexpressed in hearts of genetically hypertensive animals after brief ischemia. Differential expression between the two groups was observed after mild stimuli, but not after more severe stimuli. Cardiac hypertrophy was not a major factor for determining the overexpression of HSP72.
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PMID:Heat shock protein expression in hearts hypertrophied by genetic and nongenetic hypertension. 992 63

The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4, was injected intravenously at a dose of 1 mg kg-1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohistochemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also, compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4% +/- 11.7% of control, n = 5) as compared to vehicle group (24.2% +/- 11.8%, n = 5, p < 0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 1 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 1 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients.
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PMID:Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat. 1031 35

Heat shock proteins (HSPs) induced by brain ischemia may play an important role in neuroprotection from neuronal degeneration. In this study, we examined the cerebral blood flow (CBF) threshold to produce regional differences in HSP72 induction after transient forebrain ischemia in spontaneously hypertensive rats (SHRs). Female SHRs were subjected to 20 min of cerebral ischemia induced by bilateral carotid artery occlusion. The CBF was measured by laser Doppler flowmetry. At forty-eight hours after cerebral ischemia and reperfusion, the rats were decapitated and the brains were removed. Specific areas (hippocampal CA1, CA2-3, dentate gyrus, dorsolateral and ventromedial striatum, and parietal cortex) were thereafter dissected from the brain. The amounts of HSP72 in these samples were determined using Western blot analysis. In the hippocampus, HSP72 was induced when the CBF decreased to less than 18-25% of the resting level. The mean values of HSP72 produced in the CA1 area, CA2-3 area, and the dentate gyrus following ischemia and reperfusion treatment were 4.44 +/- 1.43 (+/-SD) ng/microg protein, 3.51 +/- 0.72 ng/microg protein and 3.77 +/- 1.05 ng/microg protein, respectively. In the parietal cortex, the amount of HSP72 induction was less pronounced (2.55 +/- 0.40 ng/microg protein), while HSP72 was hardly detected at all in the striatum, even under conditions of very severe CBF reduction and reperfusion. We demonstrated the existence of both a CBF threshold (i.e., approximately 20% of the resting level) for HSP72 induction and regional heterogeneity for the induction of HSP72 protein.
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PMID:Cerebral blood flow threshold and regional heterogeneity of heat shock protein 72 induction following transient forebrain ischemia in rats. 1034 97

Major stress protein HSP72 is known to participate in protecting cells and organisms against harmful factors including ischemia, trauma etc. Under study was the level of HSP72 in the myocardium of 32 patients with coronary disease operated in Military-medical academy. HSP72 was detected in probes of the right atria before and after pre-cardiopulmonary bypass in all cases induction of HSP72 was observed in 40% of patients, and directly correlated with the time of cardiopulmonary bypass and standing of the disease. The cardioprotective effect of the elevated pre-operational level of HSP72 was shown to be proportionate to the lower activity of cardiospecific enzymes, creatine phosphokinase (CK-MB). It is suggested that HSP72 is involved in the mechanism of cardioprotection during cardiopulmonary bypass.
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PMID:[Role of heat-shock proteins in cardioprotection of patients operated on for ischemic heart disease]. 1048 75

Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i - HSP70-1 gene and HSP70-2 gene - is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10-60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA - which was generally expressed at a far lower level than HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.
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PMID:Differential expression of heat shock proteins 70-1 and 70-2 mRNA after ischemia-reperfusion injury of rat kidney. 1055 May 16

Heat shock proteins (HSPs) may play a cardioprotective role during hypoxia or ischemia. We hypothesized that cardiac tissue from hypoxia-tolerant animals might have high levels of specific HSPs. We measured myocardial HSP60 and HSP72/73 in painted and softshell turtles during normoxia and anoxia (12 h) and after recovery (12 or 24 h). We also measured myocardial HSPs in normoxic rats and rabbits. During normoxia, hearts from the most highly anoxia-tolerant species, the painted turtle, expressed the highest levels of HSP60 (22.6+/-2.0 mg/g total protein) followed by softshells (11.5+/-0.8 mg/g), rabbits (6.8+/-0.9 mg/g), and rats (4.5+/-0.5 mg/g). HSP72/73 levels, however, were not significantly different. HSP60 levels in hearts from both painted and softshell turtles did not deviate significantly from control values after either 12 h of anoxia or 12 or 24 h of recovery. The pattern of changes observed in HSP72/73 was quite different in the two turtle species. In painted turtles anoxia induced a significant increase in myocardial HSP72/73 (from 2.8+/-0.1 mg/g normoxic to 3.9+/-0.2 mg/g anoxic, P<0.05). By 12 h of recovery, HSP72/73 had returned to control levels (2.7+/-0.1 mg/g) and remained there through 24 h (2.6+/-0.2 mg/g). In softshell turtles, HSP72/73 decreased significantly after 12 h of anoxia (from 2.4+/-0.4 mg/g normoxic to 1.3+/-0.2 mg/g anoxic, P<0.05). HSP72/73 levels were still slightly below control after 12 h of recovery (2.1+/-0.1 mg/g) and then rose to significantly above control after 24 h of recovery (4.1+/-0.7 mg/g, P<0.05). We also conclude that anoxia-tolerant and anoxia-sensitive turtles exhibit different patterns of myocardial HSP changes during anoxia and recovery. Whether these changes correlate with their relative degrees of anoxia tolerance remains to be determined.
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PMID:Expression of heat shock proteins in turtle and mammal hearts: relationship to anoxia tolerance. 1064 41

Immediate early genes and heat shock protein (HSP) 70s, which may play a role in adaptation and cellular protection, respectively, are induced by ischemia in hearts. We examined if the induction of immediate early gene (c-fos, c-myc, c-jun, and junB) and HSP70 mRNAs by ischemia is affected by ischemic preconditioning. Transient ischemia (5 or 10 minute) was applied to Wistar rat (n=75) hearts, by tightening a snare placed around left coronary arterial branches 7 days before applying ischemia. Rats without earlier ischemia (control group, C) and rats with 5-minute ischemia 12 or 24 hours earlier (EI12 or 24 group) were given 10-minute ischemia and sacrificed at 0, 0.5, 1, 2, and 4 hour. RNA was extracted from the ischemic region and Northern blot analysis was performed. The induction of c-fos and c-myc mRNAs was significantly increased in EI12 but not in EI24 compared with that in C. The induction of c-jun and junB mRNAs showed no change in both EI12 and EI24 compared with that in C. The induction of HSP72 and 73 mRNAs was decreased in EI12 and decreased further in EI24. Thus, ischemic preconditioning altered the induction of immediate early gene and HSP70 mRNAs by ischemia. The effect of preconditioning differed among genes studied and changed with time after preconditioning. Ischemic preconditioning alters protective and adaptive responses to ischemia at the gene level.
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PMID:Altered ischemic induction of immediate early gene and heat shock protein 70 mRNAs after preconditioning in rat hearts. 1073 21


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