UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patterns of expression of the bcl-2, bax, and bci-X genes were examined immunohistochemically in neurons of the adult rat brain before and after 10 min of global ischemia induced by transient cardiac arrest. High levels of the cell death promoting protein Bax and concomitant low levels of the apoptosis-blocking protein Bcl-2 were found in some populations of neurons that are particularly sensitive to cell death induced by transient global ischemia, such as the CA1 sector of the hippocampus and the Purkinje cells of the cerebellum. Moreover, within 0.5 to 3 hr after an ischemic episode, immunostaining for Bax was markedly increased within neurons with morphological features of degeneration in many regions of the brain. Use of a two-color staining method for simultaneous analysis of Bax protein and in situ detection of DNA-strand breaks revealed high levels of Bax immunoreactivity in many neurons undergoing apoptosis. Postischemic elevations in Bax protein levels in the hippocampus, cortex, and cerebellum were also demonstrated by immunoblotting. At early times after transient ischemia, regulation of Bcl-2 and Bcl-x protein levels varied among neuronal subpopulations, but from 3 hr on, those neurons with morphological evidence of degeneration uniformly contained reduced levels of Bci-2 and particularly Bci-X immunoreactivity. The findings suggest that differential expression of some members of the bcl-2 gene family may play an important role in determining the relative sensitivity of neuronal subpopulations to ischemia and that postischemic alterations in the expression of bax, bcl-2, and bcl-x may contribute to the delayed neuronal cell death that occurs during the repurfusion phase after a transient ischemic episode.
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PMID:Upregulation of bax protein levels in neurons following cerebral ischemia. 747 1

The observation that delayed death of CA1 neurons after global ischemia is inhibited by protein synthesis inhibitors suggests that the delayed death of these neurons is an active process that requires new gene expression. Delayed death in CA1 has some of the characteristics of apoptotic death; however, candidate proapoptotic proteins have not been identified in the CA1 after ischemia. We studied the expression of Bax protein and mRNA, a member of the bcl-2 family that is an effector of apoptotic cell death, after global ischemia in the four-vessel global ischemia model in the rat and compared these results with the expression of the antiapoptotic gene bcl-2. Bax mRNA and protein are both expressed in CA1 before delayed death, whereas bcl-2 protein is not expressed. Bcl-2 protein expression, but not that of Bax, is increased in CA3, a region that is ischemic but less susceptible to ischemic injury. In the dentate gyrus, both Bax and bcl-2 proteins are expressed. The selective expression of Bax in Ca1 supports the hypothesis that Bax could contribute to delayed neuronal death in these vulnerable neurons by an independent mechanism or by forming heterodimers with gene family members other than bcl-2.
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PMID:Expression of the apoptosis-effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia. 866 27

Focal cerebral ischemia in rats subjected to middle cerebral artery (MCA) occlusion results in apoptotic DNA fragmentation and activation of putative cell death effector genes in neurons and functional impairment of the plexus choroideus. In the present study we investigated whether cerebral ischemia may induce apoptotic cell death in the choroid plexus. Using in situ end-labeling by terminal transferase and fluorescein-dUTP, nuclear DNA breaks were detected in the choroid plexus of the lateral ventricle of the ischemic hemisphere after 6 h but not after 1.5 h of MCA occlusion. Intense cytoplasmic immunostaining for pro-apoptotic Bax protein and moderate immunolabeling for Bcl-X was observed in the epithelium of the choroid plexus of the lateral and third ventricles. However, constitutive expression of Bax and Bcl-X proteins in the plexus choroideus did not change significantly following focal ischemia. Thus, cells of the choroid plexus may die by apoptosis after several hours of cerebral ischemia. Modulation of cell death effector genes of the bcl-2 family however, may not be required for apoptotic cell death to occur.
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PMID:Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia. 873 34

An ischemia-reperfusion injury on the pancreas is involved in the pathophysiology of acute pancreatitis or tissue injuries after pancreas transplantation. On the other hand, recent studies have demonstrated that ischemia-reperfusion induces apoptosis in several organs such as kidney, heart, and brain. In the present study, we sought to characterize a pattern of injury during ischemia-reperfusion on the pancreas and determined whether ischemia-reperfusion on the pancreas causes the apoptotic process. Ischemia-reperfusion was induced by blocking the inferior splenic artery and removing the clamp in pentobarbital-anesthetized rats. Rats were sacrificed at 0-72 hr following a 60-min ischemia. Evans blue extravasation showed 3.5-fold increase at 2 hr after reperfusion, indicating a rapid increase of vascular permeability. Tissue myeloperoxidase activity, an index of neutrophil accumulation, significantly increased in a time-dependent manner until 48 hr after reperfusion. Histological analysis revealed the existences of interstitial cell infiltration and edema. DNA breaks of acinar cells were detected by gel electrophoresis and in situ nick end-labeling, and the numbers strikingly increased at 48 hr after reperfusion. Furthermore, Bax protein, an effector of apoptotic cell death, was expressed in acinar cells. The results indicate that an ischemia-reperfusion injury on the pancreas in rats resembles many features of acute pancreatitis. Apoptosis in acinar cells may be one of the specific features of the ischemia-reperfusion injury on the pancreas.
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PMID:Ischemia-reperfusion injury on the pancreas in rats: identification of acinar cell apoptosis. 929 80

To determine the effect of phencyclidine (a noncompetitive NMDA receptor antagonist) on expression of Bax and Bcl-2 (apoptosis-regulating proteins) in gerbil hippocampus after transient forebrain ischemia, brain sections were immunohistochemically evaluated 48, 72, 96 h and 7 days following ischemia. In ischemic control animals, the expression of Bax in CA1 neurons was increased with time and peaked at 72 h, then disappeared at 96 h. In the phencyclidine (5 mg kg-1, intraperitoneally)-treated animals, the intensity of Bax expression at 72 h was weaker than that of ischemic control animals. Furthermore, at 96 h, Bax expression was still observed in CA1 neurons. No expression of Bcl-2 in the CA1 neurons was detected in either control or phencyclidine-treated animals. From these results, it is possible that NMDA receptor antagonists exert their preventive effect against delayed neuronal death through inhibition of Bax protein expression, although the precise relationship between the function of Bax protein and delayed neuronal death is still unclear.
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PMID:Expression of Bax and Bcl-2 protein in the gerbil hippocampus following transient forebrain ischemia and its modification by phencyclidine. 942 65

Apoptosis has drawn attention in ischemic neuronal death recently. However, studies of apoptosis in cerebral ischemia have concentrated largely in DNA fragmentation, a late phase in apoptotic nuclei, at the expense of possible primary ischemic targets at the subcellular level and of upstream apoptotic signalling. To assess those issues, we used an intraluminal middle cerebral artery occlusion model in mice with or without reperfusion, and examined sequential changes of Bcl-2 family proteins modulating apoptotic signalling immunohistochemically and studied nuclear DNA fragmentation, to compare their chronology in relation to the development of infarct as detected by loss of microtubule-associated protein-2, an early marker of cytoplasmic damage. In the centre of the lesion, Bax protein increased and Bcl-2 and Bcl-x proteins decreased after loss of microtubule-associated protein-2 antigenicity occurred, but at the border of the lesion, the former changes preceded loss of microtubule-associated protein-2 antigenicity. Additionally, close morphologic analysis of DNA fragmentation in situ indicated that transient ischemia predominantly induced apoptotic cells but permanent ischemia produced necrosis of cells in the centre of the lesion. The contrasting cell death mechanisms, apoptosis and necrosis, are selectively involved in the pathology of cerebral ischemia, depending on its severity.
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PMID:Alterations of Bcl-2 family proteins precede cytoskeletal proteolysis in the penumbra, but not in infarct centres following focal cerebral ischemia in mice. 946 Jul 52

This study was performed to examine the involvement of apoptosis and the expression of bcl-2 family genes in ischemia-induced retinal injury. Retinal ischemia was induced in adult rats by raising the intraocular pressure to 130 mmHg for 45 min. Selective damage to the inner retina was observed 7 days after ischemia. No terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) positive cells were observed in the normal retina, but there was a significant number of TUNEL positive cells 6-48 h after transient ischemia followed by a decrease at 96 and 168 h. The number of TUNEL positive cells reached a maximum at 24 h after ischemia. DNA laddering was observed on agarose gel electrophoresis with the retinas 24 and 48 h after ischemia but not in the normal retina. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that bax gene expression did not change immediately after cessation of ischemia, but gradually increased as early as 6 h, reached a peak at 24 h, then decreased to near baseline levels at 168 h. On the other hand, bcl-2 gene expression showed no obvious changes at any time after transient ischemia. Moreover, intense Bax protein immunoreactivity was detected in the retinal sections at 24 h after ischemia although little immunoreactivity was present in the normal sections. These results suggest that apoptosis associated with the expression of Bax is involved in retinal cell loss after ischemic insult.
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PMID:Apoptotic DNA fragmentation and upregulation of Bax induced by transient ischemia of the rat retina. 997 17

It is well known that proteins encoded by the Bcl-2 gene family play a major role in the regulation of apoptosis. We have demonstrated previously that neuronal apoptosis can be induced in the hippocampus and striatum after global ischemia. Clenbuterol, a beta2-adrenoceptor agonist, showed considerable activity against neuronal apoptosis. In the present study, we attempted to find out whether the members of the Bcl-2 family are induced after ischemia, and whether expression of these genes could be altered by clenbuterol. Transient forebrain ischemia was performed in male Wistar rats by clamping both common carotid arteries and reducing the blood pressure to 40 mmHg for 10 min. Clenbuterol (0.5 mg/kg, i.p.) or vehicle were injected 3 h before onset of ischemia or in non-ischemic rats. The hippocampus and striatum were taken from non-ischemic rats 3, 6 and 24 h after injection of clenbuterol, as well as from drug-treated and untreated rats 6 and 24 h after ischemia. Eighty micrograms/lane total protein were loaded on a 15% sodium dodecyl sulfate-polyacrylamide gel for western blotting. Bcl-2, Bax and Bcl-xl proteins were detectable in the non-ischemic hippocampus and the striatum. Clenbuterol up-regulated the expression of Bcl-2 protein at 3, 6 and 24 h after administration. Enhanced Bcl-xl signals were found in the non-ischemic striatum 3, 6 and 24 h after clenbuterol treatment, but no change of Bcl-xl expression by clenbuterol was seen in the non-ischemic hippocampus. Bax expression was not altered by clenbuterol in the non-ischemic hippocampus and striatum. Bcl-2 was up-regulated in both detected regions at 24 h after ischemia, while the increase in Bax and Bcl-xl protein expression had appeared already at 6 h and also 24 h after ischemia. Clenbuterol further increased the expression of Bcl-2 at 6 and 24 h after ischemia. In contrast, Bax protein level was down-regulated by clenbuterol at 6 and 24 h after ischemia. Clenbuterol also increased Bcl-xl level in the ischemic striatum. The results suggest that global ischemia induces proto-oncogenes which are associated with apoptosis. Clenbuterol not only increased Bcl-2 expression in the non-ischemic hippocampus and striatum, but also up-regulated Bcl-2 and down-regulated Bax expression in the ischemic hippocampus and striatum. The increase in the ratio of Bcl-2 and Bax may contribute to the anti-apoptotic effect of clenbuterol. The present study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to interfere with neuronal damage.
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PMID:The beta2-adrenoceptor agonist clenbuterol modulates Bcl-2, Bcl-xl and Bax protein expression following transient forebrain ischemia. 1033 95

Many studies have reported ischemia protection using various preconditioning techniques, including single dose 3-nitropropionic acid (3-NPA), a mitochondrial toxin. However, the cellular signal transduction cascades resulting in ischemic tolerance and the mechanisms involved in neuronal survival in the tolerant state still remain unclear. The current study investigated the mRNA and protein expression of the antiapoptotic bcl-2 and the proapoptotic bax. two antagonistic members of the bcl-2 gene family, in response to a single dose of 3-NPA, to global cerebral ischemia-reperfusion. and to the combination of both 3-NPA-pretreatment and subsequent global cerebral ischemia-reperfusion. Brain homogenates of adult Wistar rats (n = 25) were analyzed for bcl-2 and bax mRNA expression using a new highly sensitive and quantitative polymerase chain reaction (PCR) technique that allows real-time fluorescence measurements of the PCR product (LightCycler; Roche Diagnostics, Mannheim, Germany). Animals for mRNA analysis received 3-NPA (20 mg/kg, intraperitoneal; "chemical preconditioning") or vehicle (normal saline), and were either observed for 24 plus 3 hours or were subjected to 15 minutes of global cerebral ischemia 24 hours after the pretreatment and observed for 3 hours of reperfusion. Immunohistochemistry was applied to serial brain sections of additional rats (n = 68) to determine amount and localization of the respective Bcl-2 and Bax protein expression in various brain areas. One set of animals was injected with 3-NPA and observed for 3, 12, 24, and 96 hours; a second set was exposed to 15 minutes global cerebral ischemia, 3, 12, and 24 hours reperfusion; and a third set was pretreated with 3-NPA or saline 24 hours before the ischemic brain insult and observed for 96 hours of reperfusion. The authors found single dose 3-NPA treatment to be associated with an elevated bcl-2:bax ratio (increased bcl-2 expression, decreased bax expression), both on the transcriptional (mRNA) and the translational (protein) level. The differential influence of 3-NPA was maintained during early recovery from global cerebral ischemia (3 hours), when 3-NPA pretreated animals showed higher bcl-2 and lower bax mRNA levels compared with rats with saline treatment. Respective changes in protein expression were localized predominately in neurons vulnerable to ischemic damage. Compared with baseline, Bcl-2 protein was significantly higher in surviving neurons at 96 hours after the insult, whereas Bax protein remained unchanged. However, at this late time of postischemic recovery (96 hours), the protein expression pattern of surviving neurons was not different between animals with and without 3-NPA pretreatment. To the authors' knowledge, the current study is the first report on the differential expression of pro- and antiapoptotic genes after a single, nonlethal dose of 3-NPA. The current results suggest alterations in the balance between pro- and antiapoptotic proteins as a potential explanation for the reported protection provided by chemical preconditioning using 3-NPA in rats.
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PMID:Tolerance-Inducing dose of 3-nitropropionic acid modulates bcl-2 and bax balance in the rat brain: a potential mechanism of chemical preconditioning. 1104 5

Oxidative stress plays a critical role in cardiac injuries during ischemia/reperfusion. Insulin-like growth factor-1 (IGF-1) promotes cell survival in a number of cell types, but the effect of IGF-1 on the oxidative stress has not been elucidated in cardiac muscle cells. Therefore, we examined the role of IGF-1 signaling pathway in cell survival against H2O2-induced apoptosis in H9c2 cardiac myoblasts. H2O2 treatment induced apoptosis in H9c2 cells, and pretreatment of cells with IGF-1 suppressed apoptotic cell death. The antiapoptotic effect of IGF-1 was blocked by LY294002 (an inhibitor of phosphatidylinositol 3-kinase) and by PD98059 (an inhibitor of extracellular signal-regulated kinase (ERK)). The protective effect of IGF-1 was also blocked by rapamycin (an inhibitor of p70 S6 kinase). Furthermore, H9c2 cells stably transfected with constitutively active PI 3-kinase (H9c2-p110*) and Akt (H9c2-Gag-Akt) constructs were more resistant to H2O2 cytotoxicity than control cells. Although H2O2 activates both p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), IGF-1 inhibited only JNK activation. Activated PI 3-kinase (H9c2-p110*) and pretreatment of cells with IGF-1 down-regulated Bax protein levels compared to control cells. Taken together, our results suggest that IGF-1 transmits a survival signal against oxidative stress-induced apoptosis in H9c2 cells via PI 3-kinase and ERK-dependent pathways and the protective effect of IGF-1 is associated with the inhibition of JNK activation and Bax expression.
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PMID:Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. 1122 94

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