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)

The effect of nitric oxide (NO) synthase inhibition on apoptosis of cardiomyocytes during ischemia/reperfusion was investigated. Isolated perfused guinea-pig hearts were subjected to 35 min ischemia (I) followed by 30 min reperfusion (IR) in the presence or absence of NO synthase inhibitors, L-NAME or L-NMMA or a superoxide scavenger, SOD. Apoptosis was assessed by immunohistochemistry (TUNEL assay, Bax protein staining), by spectrophotometric measurement of cytochrome oxidase activity (COX), and by ultrastructural analysis. Inhibition of NOS significantly increased apoptosis with activation of Bax protein and decrease of COX. SOD infusion had a protective effect on these apoptotic markers. The results suggest that endogenous NO synthesis during I/R protects the heart against apoptotic cell death.
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PMID:The role of endogenous nitric oxide in inhibition of ischemia/reperfusion-induced cardiomyocyte apoptosis. 1137 14

Hypothermia confers potent neuroprotection against ischemic injury. Attenuation of apoptosis by hypothermia can be one of the responsible mechanisms. In this study, in situ DNA nick-end labeling (TUNEL) and immunostaining of Bax protein were performed to evaluate the effect of postischemic hypothermia on apoptotic cell death, employing rodent transient focal ischemia. Animals received 1 hour of transient focal ischemia. Brain temperature was maintained at 37.5 +/- 0.5 degrees C during ischemia. Immediately after reperfusion, animals were assigned to either a normothermic or hypothermic group. In hypothermia, animals were cooled and brain temperature was lowered to 34.5 +/- 1.0 degrees C. Prolonged hypothermia was maintained for 16 hours and animals rewarmed. In both groups, TUNEL and immunostaining of Bax was performed. In normothermia, the number of TUNEL positive cells reached the peak at 2 days after ischemia and decreased gradually. In hypothermia, the peak was shifted to 3 days after ischemia. The number of TUNEL positive cells in hypothermia was persistently below that of normothermia. Similarly, in hypothermia, immunostaining of Bax showed attenuated immunoreactivity compared with that in normothermia. In conclusion, postischemic hypothermia reduced both the number of TUNEL positive cells and immunoreactivity of Bax, which may be one of the responsible mechanisms with which hypothermia exerts neuroprotection.
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PMID:Postischemic hypothermia attenuates apoptotic cell death in transient focal ischemia in rats. 1145 83

The authors investigated the expression of p53, p21WAF-1, and Bax proteins, and apoptosis to elucidate the cellular response to ischemia-reperfusion of the skin. The rat left lower limb was dissected at the inguinal region retaining the bone and femoral vessels, and the vessels were clamped to produce an ischemic condition. After 6 hours the clamps were removed, and the plantar skin was resected at various times up to 72 hours after reperfusion. Five skin specimens were obtained at each time point from 5 rats. When a rat died during the study, additional rats were used until five specimens could be obtained from 5 rats at each time point. The expression of the three proteins was detected by Western blot analysis. The apoptotic cells were detected using the terminal deoxytransferase-mediated dUDP nick-end labeling assay. After reperfusion, the levels of p53 and p21WAF-1 were significantly higher in the ischemia-reperfusion rats compared with the sham-operated rats. However, the levels of Bax protein did not show a noticeable increase at any period. The apoptotic cells in both the epidermis and dermis were not evident compared with the sham skin, which were similar to those in the nontreated, normal skin. These results demonstrate that p53 and p21WAF-1 proteins accumulate after 6 hours of ischemia of the skin during reperfusion. Moreover, it is speculated that accumulation of these proteins plays an important role in the survival of the skin by inducing growth arrest of the cells, but not apoptosis.
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PMID:Molecular response to ischemia-reperfusion of rat skin: study of expression of p53, p21WAF-1, and Bax proteins, and apoptosis. 1160 79

The authors investigated the expression of p53, p21(WAF-1), Bax protein, and apoptosis to elucidate the cellular response to ischemia-reperfusion of skeletal muscle using the rat lower limb model. The rat left lower limb was dissected in the inguinal region, isolating the bony femoral muscles, and the femoral vessels were clamped to produce an ischemic condition. After 3 or 6 hours, the clamps were removed and the gastrocnemius muscle was resected at various times up to 72 hours after reperfusion. Five specimens of the muscle were obtained at each time point from 5 rats. When any rat died during the study, additional rats were used until 5 specimens could be obtained from 5 rats at each time point. The expression of three proteins was detected by Western blot analysis. The apoptotic cells were detected using terminal deoxytransferase-mediated dUDP (deoxyuridine[-5']diphosphate) nick-end labeling assay. Histopathological study showed severe interstitial edema and leukocyte infiltration at 6 hours of ischemia compared with 3 hours of ischemia. Moreover, at 6 hours of ischemia, muscle fiber fragmentation was observed at 72 hours after reperfusion whereas no fragmentation was found at 3 hours of ischemia. At 3 hours of ischemia, p53 and p21(WAF-1) accumulated after reperfusion, and there was a time lag in the time of onset of elevation and the peak time point between these two proteins. The level of Bax protein did not elevate and the rate of apoptotic cells did not increase. At 6 hours of ischemia, p53 and p21(WAF-1) also accumulated, but the kinetics of p21(WAF-1) were similar to that of p53 in the time of onset of elevation and the peak time point after reperfusion. In addition, the level of Bax protein increased and apoptosis was induced. These results demonstrated that p53 and p21(WAF-1) accumulated after 3 and 6 hours of ischemia of skeletal muscle during reperfusion. Moreover, it was demonstrated that the kinetics of induced p53, p21(WAF-1) and Bax protein differ between 3 hours and 6 hours of ischemia, and it is speculated that this difference plays an important role in determining the consequence of the cell exposed to ischemia.
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PMID:Difference of molecular response to ischemia-reperfusion of rat skeletal muscle as a function of ischemic time: study of the expression of p53, p21(WAF-1), Bax protein, and apoptosis. 1177 33

This study examined the protective effects of cilostazol on cerebral infarcts produced by subjecting rats to 2-h occlusion of the left middle cerebral artery followed by 24-h reperfusion. The ischemic cerebral infarct consistently involved the cortex and striatum. The infarct size was significantly reduced, when rats received 10 mg/kg cilostazol intravenously 5 min or 1 h after the completion of 2-h ischemia. Cyclic AMP level was significantly elevated in the cortex of 4- and 12-h reperfusion (P < 0.01) following treatment with cilostazol (10 mg/kg, 5 min after 2-h ischemia) accompanied by decreased tumor necrosis factor-alpha level. Samples from the regions corresponding to the penumbra showed markedly reduced Bcl-2 protein level and, in contrast, high levels of Bax protein and cytochrome c release. Cilostazol decreased Bax protein and cytochrome c release and increased the levels of Bcl-2 protein. Cilostazol (10(-7)-10(-5) M) potently and concentration dependently scavenged hydroxyl and peroxyl radicals. In conclusion, cilostazol treatment decreases ischemic brain infarction in association with inhibition of apoptotic and oxidative cell death.
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PMID:Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. 1186 82

This study shows the preventive effect of KR-31378 [(2S,3S,4R)-N"-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine] against cerebral infarct via antioxidant and antiapoptotic actions evoked by subjecting rats to 2 h of occlusion of the left middle cerebral artery followed by 24 h of reperfusion. The brain infarct zone in the cortex and striatum of the left hemisphere was consistently identified in the cortex and striatum of the left hemisphere. The infarct area was significantly reduced after three intraperitoneal administrations of 10, 30, or 50 mg/kg KR-31378 at 5 min, 4 h, and 8 h after the completion of 2 h of ischemia. Treatment with KR-31378 (30 or 50 mg/kg) significantly reduced the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells as well as strongly suppressed the laddered feature of DNA fragmentation in the lateral cortical tissue corresponding to the penumbra. The findings of samples from penumbral zone, which showed markedly reduced Bcl-2 protein level and increased Bax protein and cytochrome c release, were wholly reversed by treatment with KR-31378. In conclusion, postischemic treatment with KR-31378 provided significant levels of cortical neuroprotection in association with inhibition of apoptotic cell death through the up-regulation of Bcl-2 expression, and the down-regulation of Bax protein and cytochrome c release.
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PMID:Neuroprotective effect of (2S,3S,4R)-N"-cyano-N-(6-amino-3, 4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine (KR-31378), a benzopyran analog, against focal ischemic brain damage in rats. 1190 75

The aim of this work was to examine factors that could be involved in the occurrence of apoptosis in rat hearts subjected to coronary occlusion followed by reperfusion. To this end, we studied the expression of the pro- and anti-apoptotic factors, bax and bcl-2, respectively, in reperfused ischemic hearts and in hearts injected with bFGF or saline. In anesthetized rats the left coronary artery was occluded for 45 min, the anesthesia withdrawn and the occlusion removed to allow reperfusion; in sham-operated rats the occlusion was omitted. After 4 hours the rats were decapitated and the heart excised. Sections from the left ventricle were stained with anti-bcl-2-antibody and anti-bax-antibody using the TUNEL method which detects apoptosis. Fragmentation of DNA isolated from reperfused ventricles was examined by agarose electrophoresis. In reperfused hearts no bcl-2 staining was observed in the discrete area in which many cardiomyocyte nuclei were stained by the TUNEL method; outside this area staining for bcl-2 was more marked than in sham-operated rats. Sections from reperfused hearts were stained for bax protein over a wide area including the apoptotic region; sham-operated hearts showed little reaction. Staining for bcl-2 was demonstrable in some nuclei in hearts from saline-injected rats; the numbers were unaffected by i. v. bFGF. Ischemia/reperfusion increases the overall expression of both bcl-2 and bax proteins, but bcl-2 is lost from the reperfused area as indicated by TUNEL staining. Accordingly, the ratio of bcl-2 to bax was reduced in the reperfused area, indicating a pro-apoptotic trend. The marked increase in bcl-2 outside the reperfused area could be a mechanism with which to salvage surviving cardiomyocytes.
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PMID:Coronary reperfusion following ischemia: different expression of bcl-2 and bax proteins, and cardiomyocyte apoptosis. 1193 25

The effects of ischemia-reperfusion (IR) and ischemic preconditioning (IP) on hemodynamics, epicardial electrography, myocardial infarct size, cardiomyocytic apoptosis and gene proteins involving apoptosis (Fas, Bcl-2 and Bax) were observed in aneasthetized rabbit myocardium. The results are as follows. (1) During ischemia-reperfusion, heart rate, arterial blood pressure and myocardial oxygen consumption were reduced progressively. The epicardial electrographic ST-segment was elevated significantly during ischemia (P<0.001)and recovered to the baseline during reperfusion. (2) The infarct size occupied 57.7+/-2.0% of the ischemic myocardium in IR group while IP reduced the infarct size to 27.7+/-1.5% (P<0.01). (3) DNA ladder pattern of ischemic myocardium was revealed by agrose gel electrophoresis in IR group while it was not found in IP group. Apoptotic cardiomyocytes were sparse within the ischemic myocardium at risk in IP as compared with those in IR heart. Apoptosis rate of the ischemic myocardium from IR and IP groups detected by flow cytometry was 11.2+/-0.4% and 6.35+/-0.2% (P<0.01), respectively. (4) Fas and Bax protein expression in the ischemic myocardium of IR and IP groups was elevated as compared with those in non-ischemic myocardium group (P<0.05). The Fas protein expression of IR group was higher than that of IP group (P<0.05). Bcl-2/Bax ratio of IR group was lower than that in non-ischemic myocardium (P<0.01). From the results, it is suggested that IP decreases cardiomyocytic apoptosis induced by IR and this action is mediated by the reduction of Fas protein expression.
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PMID:[Ischemic preconditioning reduces cardiomyocytic apoptosis in rabbit heart in vivo]. 1195 68

We focused on heat shock protein 70 (HSP70) as a marker of viability in hepatic warm ischemia-reperfusion. Segmental hepatic warm ischemia was produced in rats for 15, 30, 60, 90, 120, or 180 min. Liver sections were evaluated at 30, 60, and 120 min of reperfusion. Expression of HSP70 and messenger RNA (mRNA), apoptosis, and apoptosis-associated genes such as Bcl-2 and Bax were studied. Expression of HSP70 and mRNA was augmented as warm ischemia was prolonged, but was markedly suppressed in livers with more than 120 min of ischemia. The highest accumulation of HSP70 was observed in the nucleus. In livers subjected to longer duration of warm ischemia, necrosis and apoptosis were evident and Bcl-2 mRNA expression and Bcl-2/Bax protein ratio were markedly diminished. Apoptosis may be related to the process of cellular injury induced by warm ischemia-reperfusion. Expression of HSP70 and the Bcl-2 family can be effective markers of viability in hepatic warm ischemia-reperfusion.
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PMID:Evaluation of warm ischemia-reperfusion injury using heat shock protein in the rat liver. 1259 70

This study investigated the effects of hypothermia on apoptosis-regulating proteins in a rat model of incomplete cerebral ischemia. Twenty-seven fasted male Sprague-Dawley rats (300-420 g) were anesthetized, intubated, and mechanically ventilated with 2.0% isoflurane and N(2)O/O(2) (FiO(2) = 0.33). Catheters were inserted and cerebral blood flow velocity was measured using bilateral laser Doppler flowmetry. At the end of preparation, the administration of isoflurane was replaced by fentanyl (25 microg. kg(-1). h(-1)). Animals were randomly assigned to one of the following groups: group 1 (n = 9, normothermia), normothermia (37.5 degrees C) during ischemia; group 2 (n = 9, hypothermia), 34 degrees C pericranial temperature during ischemia; and group 3 (n = 9, sham-operated animals), normothermia, no cerebral ischemia. Ischemia (30 minutes) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure 30-35 mm Hg). Arterial blood gas tensions and pH were maintained constant. Four hours after 30 minutes of incomplete cerebral ischemia, the brains were removed for determination of the expression of the apoptosis-regulating proteins Bax, Bcl-2, p53, and Mdm-2 using immunofluorescence and Western blot analysis. Four hours after cerebral ischemia there was a significant increase in the expression of the pro-apoptotic protein Bax in normothermic animals compared with hypothermic (85-260%) and sham-operated animals (60-190%). The proteins Bcl-2, p53, and Mdm-2 showed no statistically significant differences between the groups or between the hemispheres. In conclusion, hypothermia during ischemia decreased Bax protein expression that is associated with programed cell death. This suggests that neuroprotection seen with hypothermia may be related to a reduction of pro-apoptotic events.
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PMID:The effect of hypothermia on the expression of the apoptosis-regulating protein Bax after incomplete cerebral ischemia and reperfusion in rats. 1282 67


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