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)

We investigated whether reversible oxidative stress induced by the administration of the superoxide dismutase inhibitor, diethyldithiocarbamate, could induce tolerance to subsequent cerebral ischemia in gerbil hippocampal neurons. Mature male gerbils received intraperitoneal injections of diethyldithiocarbamate (1.0 g/kg), which led to reduced superoxide dismutase activity and increases in thiobarbituric acid-reactive substance in the brain. Cerebral ischemia was produced by occluding the bilateral common carotid arteries for 5 min, either 2 or 4 days after diethyldithiocarbamate injection. One week after ischemia, samples from each brain were stained with hematoxylin-eosin to evaluate ischemic neuronal damage in the hippocampal CA1 sector. Diethyldithiocarbamate treatment 4 days before ischemia had significant protective effects against cerebral ischemia, while diethyldithiocarbamate 2-day pretreatment and vehicle treatment failed to show neuroprotection. Biochemical examinations showed a clear induction of heat shock protein 72 and a significant increase in manganese-containing superoxide dismutase in the hippocampus in animals treated with diethyldithiocarbamate 4 days prior to ischemia. These results suggested that the oxidative stress caused by diethyldithiocarbamate could induced tolerance to ischemia in the gerbil brain, and that the increase in the biosynthesis of manganese-containing superoxide dismutase and heat shock protein 72 could provide a biochemical explanation of the tolerance induced under these conditions.
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PMID:Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons. 133 59

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.
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PMID:'Ischemic tolerance' phenomenon detected in various brain regions. 180 39

The major mammalian stress-inducible protein, heat shock protein 72, protects cells from certain stresses and rapidly accumulates in cells after ischemia. Heat shock protein 72 is rapidly synthesized in the myocardium of various species in response to ischemia, but it has not been investigated in human heart. To determine if heat shock protein 72 accumulated in the ischemic myocardium of patients undergoing cardiac operations, we obtained sequential right atrial biopsy specimens from 12 patients undergoing repair at three intervals: before bypass, after reperfusion, and after bypass. Immunoblot analysis for heat shock protein 72 demonstrated a high expression in the human heart compared with other mammalian hearts, p (Binomial) = 0.01. Compared with before bypass, heat shock protein 72 contents after reperfusion and after bypass were 98.2% +/- 8.9%, p (signed-rank) = 0.65, and 87.6% +/- 17.1%, p (signed-rank) = 0.28, respectively. Although heat shock protein 72 concentration was unchanged in hearts after reperfusion and after bypass, the initial prebypass level of heat shock protein 72 was high. The high heat shock protein 72 level detected in human hearts may reflect preoperative disease and drug therapy, or inherently high levels may be usual in the human myocardium. These findings indicate that the myocardium of patients undergoing cardiac operations contains relatively high concentrations of heat shock protein 72, which are not increased during the surgical procedure.
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PMID:Heat shock protein (HSP 72) expression in patients undergoing cardiac operations. 785 89

Brief periods of non-lethal cerebral ischemia can induce resistance against subsequent lethal ischemia. In this study, asymptomatic gerbils after unilateral carotid artery ligation were subjected to 5 min of forebrain ischemia. The prolonged but mild hypoperfusion, by carotid occlusion, induced susceptibility at 1 day and tolerance at 30 days to lethal ischemia in the hippocampal neurons. The neuroprotective effect correlated well with induction of heat shock protein 72 in the hippocampal neurons. These results suggested that neuronal cells possess a cellular response to sublethal hypoperfusion and can survive forthcoming ischemic stress.
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PMID:Induced resistance and susceptibility to cerebral ischemia in gerbil hippocampal neurons by prolonged but mild hypoperfusion. 834 18

Induction of stress proteins is thought to be important in the protection of cells from a variety of environmental insults including heat, hypoxia and ischemia. The aim of this study was to compare the mechanism of induction of heat shock protein 72 (HSP72) in primary cultures of murine cortical astrocytes by heat and combined oxygen-glucose deprivation (OGD), a model of in vitro ischemia. 35S-methionine labeling and immunoblotting showed increased HSP72 synthesis and accumulation lasting for up to 24 h following heat or OGD. Heat induced a markedly greater amount of HSP72 mRNA and protein than did OGD. We then sought evidence of heat shock transcription factor-1 (HSF-1) activation. An increase in apparent molecular weight of nuclear HSF-1 after heat or OGD was observed, consistent with increased phosphorylation. To seek an explanation of the difference between heat and OGD as inducers of HSP72 we examined the binding activity of HSP72 + 73 to other proteins. More cellular protein was found to co-immunoprecipitate with HSP72 + 73, and more HSP72 + 73 was found in the pellet fraction after heat shock compared to OGD. These results suggest that HSP72 induction is regulated in astrocytes at least in part at the level of HSF activation, by both heat and OGD. Reduced availability of free HSP72 + 73 in heated cells could be responsible for the greater magnitude of HSP72 induction after heat compared to OGD.
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PMID:Mechanism of heat shock protein 72 induction in primary cultured astrocytes after oxygen-glucose deprivation. 871 40

The authors have shown that stimulation of cardiac alpha 1-adrenoceptors confers immediate cardioprotection in the isolated rat heart against post-ischemic dysfunction, and have recently demonstrated that in vivo treatment of rats with norepinephrine (NE) induces cardiac heat shock protein 72 and myocardial adaptation to ischemia 24 h after treatment. To characterize the delayed myocardial adaptive response induced by NE further, the present study examined its time course and effects of adrenoceptor antagonism and protein synthesis inhibition on this adaptive response during optimal myocardial protection. Rats were treated with NE (3.1 mumol/kg, i.p.) or normal saline (0.4 ml, i.p.), and hearts isolated at 2, 4, 24, 72 and 168 h after injection. Isolated hearts were subjected to 25 min of normothermic global ischemia and 40 min of reperfusion by the Langendorff technique, and left ventricular developed pressure (LVDP) was assessed. There was no difference in baseline LVDP among groups. Post-ischemic LVDP recovered to 44.7 +/- 2.1 mmHg in pooled saline control. LVDP was significantly improved in hearts isolated at 4, 24 and 72 h after injection of NE (66.3 +/- 3.8, 68.6 +/- 2.7 and 72.6 +/- 8.3 mmHg, respectively, P < 0.05 v control) but not in hearts isolated at 2 or 168 h. Effects of antecedent adrenoceptor antagonism and protein synthesis inhibition were examined in hearts isolated at 72 h after NE treatment. Prazosin pretreatment (2.4 mumol/kg, i.p.) abolished the delayed myocardial adaptive response induced by NE at 72 h (post-ischemic LVDP 48.3 +/- 6.1 mmHg, P > 0.05 v control) while propranolol pretreatment (3.4 mumol/kg, i.p.) had no effect (post-ischemic LVDP 67.3 +/- 3.7 mmHg, P < 0.05 v control). Cycloheximide pretreatment (3.6 mumol/kg, i.p.) also abolished the beneficial effect of NE at 72 h (post-ischemic LVDP 50.2 +/- 6.0 mmHg, P > 0.05 v control). In conclusion, administration of NE to rats can induce delayed and sustained cardioprotection against post-ischemic myocardial dysfunction. NE-induced myocardial adaptation to ischemia at 72 h is mediated by alpha 1-adrenoceptors and appears to require protein synthesis.
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PMID:Norepinephrine-induced sustained myocardial adaptation to ischemia is dependent on alpha 1-adrenoceptors and protein synthesis. 889 60

We evaluated the mechanism of the heat shock-induced tolerance to ischemia-reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a 1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after 40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04 microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased markedly after heat shock exposure. The release of creatine kinase (CK) from the myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2: 7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP: 11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg protein), but not hsp72, and abolished the heat shock-induced decrease in CK release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction, plays a pivotal role in the heat shock-induced acquisition of tolerance to hypoxia-reoxygenation in neonatal rat cardiac myocytes.
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PMID:Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia-reoxygenation injury. 923 35

We compared the time course of tolerance to myocardial ischemia-reperfusion injury with the time course of heat shock protein 72 (hsp72; inducible form) induction after heat stress in a rat model. The size of the infarct resulting from ischemia-reperfusion was increased 12 h after whole-body hyperthermia (42 degrees C for 15 min), but was significantly decreased 48 and 72 h after hyperthermia, compared with the sham control. The infarct size was decreased as late as 96 h after hyperthermia, although the infarct-limiting effect was smaller at that time. The myocardial content of hsp72 was markedly increased for 3-72 h after hyperthermic treatment, and was decreased after 72 h in association with an increase in the infarct size. The hsp72 content remained elevated during the period of tolerance to ischemia-reperfusion injury, but the infarct size decreased after the hsp72 content peaked. Pretreatment with a protein kinase C (PKC) inhibitor, chelerythrine chloride, immediately before hyperthermia, significantly suppressed the delayed cardioprotective effect of hyperthermia and reduced hsp72 induction. These results suggest that newly synthesized hsp72 through PKC activation after heat stress may have to be post-translationally modified and compartmentalized prior to assuming to the development of the delayed tolerance to ischemia-reperfusion injury in rats.
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PMID:Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart. 923 36

The decreased tolerance of steatotic livers to warm ischemia complicates liver surgery. The efficacy of heat shock preconditioning in steatotic livers to lessen ischemia-reperfusion injury was studied in rats. Steatotic liver was produced in Lewis rats with a choline-deficient diet. Rats with steatotic livers were divided into a heat shock preconditioned group (group HS) and a control group (group C). All rats received 45 min of hepatic warm ischemia. Survival rates and changes in biochemical and histological parameters were compared in both groups. Heat shock protein 72 (HSP72) was produced only in group HS. The 7-day survival of the rats after warm ischemic intervention was significantly better in group HS (13/15) than in group C (5/15) (P < 0.01). The concentration of ATP in liver tissue (n = 10, P < 0.01) and serum levels of aspartate aminotransferase (n = 10, P < 0.05), alanine aminotransferase (n = 10, P < 0.01), and lactic dehydrogenase (n = 10, P < 0.01) at 40 min reperfusion were also significantly better in group HS than in group C. Histological examination at 40 min reperfusion showed severe sinusoidal congestion, hepatocyte necrosis, and increased positivity to 4-hydroxy-2-nonenal-modified proteins in group C livers; these signs were markedly suppressed in group HS livers. The data indicate that heat shock preconditioning provides the steatotic rat liver with significant tolerance to warm ischemia-reperfusion injury.
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PMID:Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers. 973 39

A replication defective adenoviral vector containing the E. coli lacZ gene (AdCMVnLacZ) was directly injected into right hippocampus and lateral ventricle immediately after 5 min of transient global ischemia in gerbils. The relations between the lacZ gene expression and DNA fragmentation or heat shock protein 72 (HSP72) immunoreactivity were examined up to 21 days post ischemia. The lacZ gene was transiently expressed at 1 day in the hippocampus except around the CA1 region, while a large number of the periventricular cells strongly expressed the lacZ gene from 8 h to 7 days. In CA1 layer, terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) positive cells, which were present only adjacent to the needle track at 8 h to 1 day, became more extensive in the whole CA1 layer at 3 to 7 days. TUNEL-positive cells were also detected around the DG at 1 day, around the needle track at 8 h to 3 days, and in the choroid plexus cells at 7 days. HSP72 staining was detected in the subiculum at 1 to 3 days, the dentate granule cells at 8 h to 1 day, and in the CA3 or CA4 pyramidal cells at 1 to 3 days. Some lacZ expressing cells were double-positive with HSP72 in DG, while the majority of those were distinguished from the TUNEL-positive cells. Pyramidal neurons were almost completely lost in the CA1 sector at 7 days after the ischemia. The present study demonstrates the successful LacZ gene transfer into the hippocampus and ventricle of postischemic gerbil brain except in the vulnerable CA1 layer by adenoviral vector injection. However, adenovirus-mediated gene transfer may induce indirect apoptotic cell death in the DG and ventricle, in addition to direct traumatic injury around the needle track.
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PMID:DNA fragmentation and HSP72 gene expression by adenovirus-mediated gene transfer in postischemic gerbil hippocampus and ventricle. 980 66


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