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)

An ischemia-mimicking metabolic stress in cultured endothelial cells from the human aorta or umbilical vein caused ATP depletion, a rise in cytosolic free Ca2+, fragmentation and aggregation of actin microfilaments, retraction of the cytoplasm, and disintegration of cell monolayer. Simultaneously, the constitutive heat shock protein 27 (HSP27) underwent dephosphorylation and formed granules inside cell nuclei. Prior heat shock (45 degreesC, 10 min) in confluent cultures conferred two phases (early and delayed) of tolerance to simulated ischemia. Although heat preconditioning did not retard the ATP drop and the free Ca2+ overload within ischemia-stressed cells, each phase of the tolerance was manifested in longer preservation of normal cell morphology during the stress. Cells exhibiting the early tolerance within 3 h after heating altered the F-actin response to ischemic stress; no microfilament debris but, instead, translocation of F-actin to the tight submembranous layer was observed. In contrast, the delayed cytoprotection preserved the preexisting F-actin bundles under simulated ischemia; this happened only after 12- to 14-h post-heat shock recovery, elevating the intracellular HSP content, and was sensitive to blockers of HSP synthesis, cycloheximide and quercetin. The dephosphorylation and intranuclear granulation of HSP27 were markedly suppressed in both phases of the heat-induced tolerance. Without heat pretreatment, similar attenuation of the HSP27 dephosphorylation/granulation and the actin cytoskeleton stability during simulated ischemia were achieved by treating cells with the protein phosphatase inhibitors cantharidin or sodium orthovanadate. We suggest that prior heat shock ameliorates the F-actin response to ischemic stress by suppressing the HSP27 dephosphorylation/granulation; this prolongs a sojourn in the cytosol of phosphorylated HSP27, which protects microfilaments from the disruption and aggregation.
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PMID:Early and delayed tolerance to simulated ischemia in heat-preconditioned endothelial cells: a role for HSP27. 984 15

Ischemic preconditioning (PC) induces delayed phase of protection, known as the second window of protection (SWOP). We investigated this phenomenon in rat and correlated it with the expression of 72-kDa heat shock protein (HSP 72). Rats were preconditioned with 1, 2, and 3 cycles of 5-min left anterior descending artery occlusions, each separated by a 10-min reperfusion (PC x 1, PC x 2 and PC x 3, respectively). Another group of rats was preconditioned with heat shock (HS) by raising temperature to 42 degreesC for 15 min. Twenty-four hours later, rats were given sustained ischemia for 30 min and 90 min of reperfusion. Infarct sizes (%risk area) were 40.0 +/- 7.5, 37.6 +/- 5.6, and 47.6 +/- 2.4 (mean +/- SE) for PC x 1, PC x 2, and PC x 3 hearts, respectively, which were not different from the sham (49.9 +/- 3.9, P > 0.05). In contrast, infarct size was reduced from 47.5 +/- 3.8% in sham to 4.7 +/- 2.3% (P < 0.01) 24 h after HS. Additionally, early PC significantly reduced infarct size from 47.5 +/- 3.8% in controls to 6.0 +/- 1.2 and 5.0 +/- 1.1% with PC x 1 and PC x 3. Repeated PC cycles induced over a threefold increase in HSP 70 mRNA after 2 h compared with sham (P < 0.05). HSP 72, which increased 24 h after PC or HS, was not significantly different between the two PC stimuli. We conclude that PC does not induce SWOP in rat heart despite enhanced expression of HSP 72. In contrast, HS-induced delayed protection was associated with enhanced accumulation of HSP 72. It is possible that SWOP and HS have distinct mechanisms of protection that may not be exclusively related to HSP 72 expression.
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PMID:Induction of 72-kDa heat shock protein does not produce second window of ischemic preconditioning in rat heart. 988 36

The aim of this study was to determine the effects of acute bouts of exercise on myocardial recovery after ischemia and heat shock protein expression. Adult female Sprague-Dawley rats were divided into five groups: 1) 1-day run (1DR; n = 6) and 2) 3-day run (3DR; n = 7), in which rats ran for 100 min at a speed of 20 m/min up a 6 degrees grade for 1 or 3 consecutive days; 3) 1-day cold run (1CR), in which rats ran the same as 1DR but with wet fur at 8 degrees C, which prevented an elevation of core temperature (n = 8); 4) heat shock sedentary (HS), in which rats had their core temperatures raised to 42 degrees C one time for 15 min (n = 5); and 5) sedentary control (n=15). Cardiac function was analyzed 24 h after the last treatment using an isolated, working heart model. Nonpaced hearts were initially perfused under normoxic conditions, then underwent 17 min of global, normothermic (37 degrees C) ischemia, and, finally, were allowed to recover for 30 min under normoxic conditions. The concentration of the 72-kDa heat shock protein (HSP 72) was measured in each left ventricle. Compared with that in the sedentary group, recovery of cardiac output x systolic pressure (CO x SP) was enhanced (P < 0.05) in all treatment groups when the postischemic value was covaried with the preischemic value. No differences in CO x SP were found (P > 0.05) between the following groups: 1DR vs. 3DR, 1DR vs. HS, and 1DR vs. 1CR. Heat shock protein concentration was significantly greater (P < 0.05) than that in the sedentary controls in HS, 1DR, and 3DR groups, but not for 1CR. The concentration of HSP 72 was not significantly correlated with postischemic CO x SP (R2 = 0.197, P > 0.05). We conclude that acute bouts of exercise can produce cardioprotective effects without an elevation of HSP 72.
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PMID:Acute exercise can improve cardioprotection without increasing heat shock protein content. 1007 97

Heat stress (HS) and the subsequent expression of 72 kDa heat shock protein (HSP 72) has been shown to enhance post-ischemic functional recovery and reduce infarct size. Because the synthesis of heat shock proteins involves activation of heat shock transcription factors through phosphorylation, we hypothesized that inhibition of protein kinase C (PKC) would block HS mediated protection and expression of HSP 72 in the heart. Five groups of rats were studied (1) Sham anesthetized, (2) HS group--animals were heat shocked by raising the whole body core temperature to 42 degrees C for 15 min, (3) Vehicle group--HS rats treated with 50% DMSO in saline, (4) PKC inhibitor-treated group--specific PKC antagonist, chelerythrine chloride (5 mg/kg, i.p) given 30 min prior to HS and (5) Vehicle treated control--non-HS rats treated with vehicle prior to ischemia/reperfusion. Hearts were subjected to 30 min of regional ischemia and 90 min of reperfusion 24 h after HS. Risk area was delineated by injection of 10% Evan's blue and infarct size determined using computer morphometry of tetrazolium stained sections. Infarct size (% area at risk) reduced significantly from 49.4 +/- 2.3% (n = 7) in sham to 10.0 +/- 2.5% (p < 0.01) and 9.1 +/- 3.0% in HS and vehicle treated HS groups respectively (p < 0.05) Treatment with chelerythrine prior to HS increased infarct size to 49.4 +/- 2.3% (p < 0.05). Infarct size in chelerythrine-treated non-HS ischemic/reperfused heart was 40.7 +/- 5.4%, which did not differ significantly from vehicle-treated sham group. Western blot analysis demonstrated marked increase in HSP 72 in HS groups (with or without vehicle treatment) and pretreatment with chelerythrine chloride failed to inhibit the expression of HSP 72. The results suggest that HS-induced ischemic tolerance is mediated via PKC pathway and this protection does not appear to be directly related to the expression of HSP 72 in rat heart.
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PMID:Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. 1039 76

The adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) induces delayed ischemic protection in vivo. We hypothesized that this protection is mediated by opening of ATP-sensitive K(+) (K(ATP)) channels and increased synthesis of 72-kDa heat shock protein (HSP 72). Six groups (n = 9-13 animals/group) of animals were studied: group I, control rabbits that received no treatment; group II, animals given glibenclamide (0.3 mg/kg iv) 30 min before ischemia; group III, animals given 5-hydroxydecanoate (5-HD; 5 mg/kg iv) 15 min before ischemia; group IV, rabbits treated with CCPA (0.1 mg/kg iv) 24 h before ischemia; and groups V and VI, CCPA-treated animals that received the K(ATP)-channel blockers glibenclamide or 5-HD, respectively, 30 or 15 min before ischemia. All animals were subjected to ischemia by 30 min of coronary artery occlusion followed by 3 h of reperfusion. Risk area was delineated by injection of 10% Evans blue dye, and infarct size was determined by triphenyltetrazolium staining. Action potential duration (APD) was measured with an epicardial electrode. HSP 72 was measured by Western blotting. CCPA caused a significant reduction in infarct size [12.02 +/- 1.0 vs. 40.0 +/- 3.8% (%area at risk) in controls, P < 0.01] that was blocked by glibenclamide (36.2 +/- 3.1%, P < 0.01) and 5-HD (35.0 +/- 2.9%, P < 0.01). Glibenclamide and 5-HD did not change infarct size in control rabbits. These blockers significantly suppressed ischemia-induced APD shortening in control and CCPA-treated animals. CCPA treatment did not induce HSP 72 in hearts. These data suggest that adenosine-initiated delayed protection is mediated via opening of K(ATP) channels but does not involve the synthesis of HSP 72.
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PMID:Delayed preconditioning with adenosine is mediated by opening of ATP-sensitive K(+) channels in rabbit heart. 1040 90

Heat shock (HS) and 4-monophosphoryl lipid A (MLA, a non-toxic analogue of endotoxin) protects the myocardium against ischemia-reperfusion injury. We studied the involvement of ATP-sensitive potassium channel (KATP channel) in ischemic protection induced by these stimuli. Anesthetized rabbits were preconditioned with either HS (by raising temperature to 42 degrees C for 15 min) or intravenous pretreatment with MLA (35 micrograms/kg). After 24 h, animals were re-anesthetized and subjected to 30-min regional ischemia followed by 180-min reperfusion (I/R). KATP channel blockers glibenclamide and/or 5-hydroxydecanoate (5-HD) were used to inhibit channel function. The 72 kD heat shock protein (HSP-72) was measured by Western blots. HS produced a marked reduction in infarct size (39.4 +/- 8.1% to 14.3 +/- 2.5%, p < 0.05) that was abolished by glibenclamide (42.3 +/- 3.2%) and 5-HD (33.7 +/- 4.8%) when given before I/R. These drugs failed to block HS protection when given before HS. Expression of HSP-72 was increased in all HS groups as compared to non-HS groups in both glibenclamide and 5-HD-treated rabbits. Similarly, pretreatment with MLA reduced infarct size from 40 +/- 8.6% to 15.1 +/- 1.5% (p < 0.05). The infarct size increased to 51.9 +/- 5.8 with 5-HD in MLA-treated rabbits. 5-HD did not alter infarct size significantly when given in vehicle-treated control rabbits. These data suggest that HS and MLA exert their anti-ischemic effect through activation of KATP channel.
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PMID:Role of KATP channel in heat shock and pharmacological preconditioning. 1041 33

We have shown that isolated blood-perfused heat-stressed hearts are protected only when the blood donor animal has not been exposed to hyperthermia. Systematic hyperthermia results in larger infarction of both isolated control and heat-stressed hearts. In this study we investigated whether indomethacin inhibits in vivo the detrimental effect of hyperthermia. Male rabbits were divided into four groups, that is A(30), B(30), C(30), and D(30), representing hearts that ultimately received 30 minutes of ischemia. In a second series, rabbits were divided into groups A(45), B(45), (C45), and D(45) representing hearts that ultimately received 45 minutes of ischemia, and in a third series were divided into groups A(HSP), B(HSP), C(HSP), and D(HSP) representing animals that were heat shocked and their hearts were used to measure heat shock proteins. All the A groups (heat shocked) were subjected to 42 degrees C hyperthermia, all the B groups to the same procedure but with the addition of indomethacin (heat shocked + indomethacin), all the C groups served as controls, and all the D groups were treated with indomethacin only (control + indomethacin). Twenty-four hours later, all (30) and (45) groups were subjected to ischemia, whereas hearts from all (HSP) groups were harvested for heat shock protein measurements. When the animals were exposed to 30-minute ischemia, a significant difference in the infarcted to risk zone ratio (%I/R) was observed: A(30): 33.0 +/- 5.2, B(30): 16.1 +/- 4.4 [conferring a 51.2% reduction in infarct size, P < 0.05], C(30): 48.9 +/- 4.0, and D(30): 47.8 +/- 3.8 [P < 0.001 vs. B (30) and P < 0.05 vs. A(30)]. However, the %I/R did not differ among any of the (45) groups. Heat shock proteins themselves were seen to increase in A(HSP) and B(HSP) groups. Indomethacin enhances the beneficial effect of heat shock after 30-minute ischemia in vivo, reducing the infarct size by 51.2% in comparison with heat shock.
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PMID:Enhanced protection of heat shock in myocardial infarction: inhibition of detrimental effect of systemic hyperthermia. 1043 85

The findings of troponin I (TnI) proteolysis (in isolated rat hearts) and induction of selected sarcoplasmic reticulum (SR) calcium-regulatory genes (after repetitive total coronary occlusions in swine) have given rise to the hypothesis that the time course of functional recovery of stunned myocardium reflects the resynthesis of reversibly damaged proteins. Although stunning occurs after brief total occlusions and prolonged partial occlusions (ie, short-term hibernation), the time course of functional recovery varies from a few hours to several days, suggesting that the severity of protein damage or mechanisms responsible for the dysfunction may differ. To study this, we examined SR gene expression and TnI degradation in stunned myocardium produced by 10-minute total left anterior descending coronary artery (LAD) occlusions (n=4) or 1-hour partial LAD occlusions, in which flow was reduced to approximately 50% of control values for 60 minutes (n=6) in swine. One hour after reperfusion, LAD wall thickening was severely depressed in both models despite normal perfusion and no triphenyltetrazolium chloride evidence of necrosis. Normal myocardium exhibited TnI immunoreactivity at 31 kDa and a weak secondary band at 27 kDa. Irreversible injury or calpain activation in vitro produced a marked increase in the intensity of the 27-kDa band, consistent with TnI degradation. Stunned myocardium demonstrated no change in the 31- or the 27-kDa band, and the percentage of the 27- to 31-kDa band remained constant after 10-minute total occlusions (LAD, 5.9+/-0.9%; normal, 4.9+/-1.6%) and 1-hour partial occlusions (LAD, 8.5+/-1.9%; normal, 7.3+/-1.4%) and in sham controls (LAD, 10.9+/-1.5%; normal, 9.8+/-1.4%). Northern analysis showed no alterations in TnI or SR gene expression, but the stress protein HSP-70 was variably induced. Thus, stunned myocardium occurs without TnI degradation or altered SR gene expression, indicating that additional mechanisms are responsible for the reversible dysfunction after single episodes of regional ischemia in swine.
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PMID:Absence of troponin I degradation or altered sarcoplasmic reticulum uptake protein expression after reversible ischemia in swine. 1047 76

Potential long-term cardioprotection was investigated in an extensive experimental study. Lactobacillus cultivation components (LCC) were administered intravenously in anesthetized rats 1, 7, and 21 days before global ischemia (GI). GI was produced by full stop flow in isolated Langendorff-perfused hearts for 20 min and was followed by reperfusion. Control animals were injected with saline. LCC reduced reperfusion tachyarrhythmia significantly and improved functional recovery of the ischemized rat heart. These beneficial effects were associated with reduction of release of norepinephrine (NE) and prostacyclin at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70-kDa heat stress protein (HSP-70) at ischemia and reperfusion (P < 0.05). This cardioprotection was documented up to 21 days after a single injection of LCC. Thus Lactobacillus cultivation components are new nontoxic materials that produce marked long-term cardioprotection against ischemia-reperfusion damage. This effect is attributed to an activation of the cellular defense system, manifested by activation of the antioxidant pathway and by expression of protective proteins. NE is involved in this process, and the data also suggest a role for prostacyclin in this model of cardioprotection. The potential of LCC and related compounds working through similar mechanisms in the prevention and therapy of various ischemic heart syndromes should be explored.
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PMID:A new method of long-term preventive cardioprotection using Lactobacillus. 1077 53

1. The present study was designed to examine the regional expression of HSP72/73 protein after a 7.5-min period of cerebral ischemia and to compare the distribution of HSP neurons with the localization of irreversible neuronal degeneration as analyzed by silver impregnation technique. 2. During 6-24 hr after cerebral ischemia clear-cut neuronal argyrophilia developed in several brain regions including the hippocampal hilus, nucleus reticularis thalami, and colliculi inferiores. With the exception of the hippocampal hilus, the structures which showed silver impregnability were HSP72 negative at 6-24 hr. 3. Despite the clear HSP72 expression seen in hippocampal CA1 neurons, a significant loss of these neurons was seen at 7 days after ischemia. 4. These data show that in some structures the presence of HSP72 is indicative of higher resistance of these neurons to ischemia-induced degeneration, however, the process of delayed neuronal degeneration appears to be independent of the accelerated synthesis of HSP72 seen during the early period of reflow.
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PMID:Time course of brain neuronal degeneration and heat shock protein (72) expression following neck tourniquet-induced cerebral ischemia in the rat. 1078 34


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