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)

In order to study the effects of ethyl pyruvate on cardiomyocyte apoptosis following ischemia/reperfusion (I/R) in vitro and the expression of Bcl-2 and Bax proteins, isolated rat hearts were perfused in a Langendorff model. Twenty-four rats were randomly divided into 3 groups (n=8 in each group): control group was perfused for 120 min. In the I/R group, after 30 min stabilization the injury was induced by 30 min global ischemia followed by 60 min reperfusion. Ethyl pyruvate (EP) group was set up with the same protocol as I/R group except that it was supplied with 2 mmol/L EP 15 min before ischemia and throughout reperfusion. Myocardial malonaldehyde (MDA) content was measured. Myocardial apoptotic index (AI) was tested by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in cardiac myocytes was detected by immunohistochemistry. As compared with control group, the content of MDA, myocardial AI and the expression of Bcl-2, Bax proteins were increased significantly in I/R group, but the content of MDA, myocardial AI and the expression of Bax protein were decreased obviously and the expression of Bcl-2 protein was up-regulated in EP group (P<0.05). These results demonstrate that EP could inhibit apoptosis of cardiac myocytes possibly via alleviating oxidative stress, up-regulating Bcl-2 and down-regulating Bax proteins.
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PMID:Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. 1856 23

This study examined whether or not the ER stress and Bcl-2 proteins are linked to the protective effect of kaempferol, a phytoestrogen, on ischemia-reperfusion (I/R)-induced cardiac damage. In order to determine if kaempferol modifies the I/R-induced response in H9c2 cardiac muscle cells, the cells were exposed to kaempferol followed by ischemia 12h/reperfusion 4h. kaempferol had a protective effect on the apoptosis induced by I/R in the cardiac muscle cells. The Kaempferol treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased the level of the pro-apoptotic protein, bax. Kaempferol down-regulated the expressions of the endoplasmic reticulum (ER) stress proteins, GRP78, ATF-6alpha, XBP-2, IRE1-alpha, phosphor-eIF-2alpha and CHOP. In ex vivo-Langendorff experiment, the kaempferol treatment regulated the expression of ER stress proteins-CHOP and GRP78. The kaempferol also improved the post-ischemic LVEDP and LVDP significantly after 20, 30, 40 and 50 min of reperfusion compared with the untreated control hearts, which shows that kaempferol offers protection against I/R-associated cardiac dysfunction.
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PMID:Kaempferol protects ischemia/reperfusion-induced cardiac damage through the regulation of endoplasmic reticulum stress. 1856 83

Loss of retinal ganglion cells occurs in a variety of pathological conditions, including central retinal artery occlusion, diabetes and glaucoma. Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure (IOP), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase Akt and activation of GSK-3beta followed, during reperfusion, by a longer lasting, PI3K-dependent, activation of Akt and phosphorylation of GSK-3beta. Under these experimental conditions, retinal ischemia induced the expression of Bad, a pro-apoptotic protein, member of the Bcl-2 family. The detrimental effects yielded by the ischemic stimulus were minimized by intravitreal administration of the NMDA receptor antagonist, MK801, that reduced the expression of Bad and significantly increased Akt phosphorylation. In conclusion, our present results contribute to unravel the mechanisms underlying retinal damage by high IOP-induced transient ischemia in rat. In addition, these data implicate the pro-survival PI3K/Akt pathway and the observed reduced expression of Bad in the neuroprotection afforded by MK801.
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PMID:Modulation of pro-survival and death-associated pathways under retinal ischemia/reperfusion: effects of NMDA receptor blockade. 1880 92

Remifentanil is a commonly used opioid in anesthesia with cardioprotective effect in ischemia-reperfused (I/R) heart. We evaluated the influence of remifentanil on myocardial infarct size and expressions of proteins involved in apoptosis in I/R rat heart following various time protocols of remifentanil administration. Artificially ventilated anesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Rats were randomly assigned to one of five groups; Sham, I/R only, remifentanil preconditioning, postconditioning and continuous infusion group. Myocardial infarct size, the phosphorylation of ERK1/2, Bcl2, Bax and cytochrome c and the expression of genes influencing Ca2+ homeostasis were assessed. In remifentanil-administered rat hearts, regardless of the timing and duration of administration, infarct size was consistently reduced compared to I/R only rats. Remifentanil improved expression of ERK1/2 and anti-apoptotic protein Bcl2, and expression of sarcoplasmic reticulum genes which were significantly reduced in the I/R rats only. Remifentanil reduced expression of pro-apoptotic protein, Bax and cytochrome c. These suggested that remifentanil produced cardioprotective effect by preserving the expression of proteins involved in anti-apoptotic pathways, and the expression of sarcoplasmic reticulum genes in I/R rat heart, regardless of the timing of administration.
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PMID:Remifentanil protects myocardium through activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart. 1968 51

Integrin alpha(v)beta(8) plays an important role in cerebral vascular development. It has been proven that alpha(v)beta(8) is a key factor for transforming growth factor-beta1 (TGF-beta1) activation in epithelial cells. However, it is not clear whether alpha(v)beta(8) can activate TGF-beta1 and play a role in protection during neonatal hypoxic-ischemic brain injury. In this study, we investigated the relationship between alpha(v)beta(8) and TGF-beta1 activation, and thus the effects of TGF-beta1 activation in the protection of neurons after hypoxia-ischemia (HI). Astrocytes and neurons from rat brains were cultured and then subjected to oxygen-glucose deprivation to generate HI model in vitro. beta(8) expression was determined using immunocytochemistry, western blot, and reverse-transcriptase polymerase chain reaction. TGF-beta1 activation was determined by TGF-beta bioassay in a tested cell (astrocyte) and a reporter cell co-culture system. The pro-apoptotic protein, cleaved caspase-3, and the anti-apoptotic protein, Bcl-2 and Bcl-xL, were detected using western blot. Cellular apoptosis was detected with TUNEL. We found that beta(8) expression was stronger in astrocytes than that in neurons under normoxia. HI resulted in a rapid and persistent increase of beta(8) expression in astrocytes, but only in a slight and transient increase in neurons. Astrocytes beta(8) could induce TGF-beta1 leading to upregulation of Bcl-2 and Bcl-xL, and thus attenuated neuronal apoptosis. The present findings suggest that beta(8) protecting the brain against neonatal HI injury through TGF-beta1 signaling pathway, which may have implications for the treatment of HI brain injury.
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PMID:The role of integrin alpha(v)beta (8) in neonatal hypoxic-ischemic brain injury. 1977 86

The therapy for acute myocardial infarction (AMI) has been improved; yet, AMI remains a major cause of death and heart failure in industrialized countries. B-type natriuretic peptide (BNP), a hormone secreted from the heart, has been shown cardioprotective effects during myocardial ischemia/reperfusion. In the present study, we aimed to examine whether BNP could inhibit myocardial apoptosis during ischemia/reperfusion. Rabbits were randomly divided into three groups (12 animals for each group): sham-operated control and ischemia-reperfusion animals with or without BNP treatment. Occlusion of the left circumflex coronary for 45 min was followed by 3-h reperfusion with infusion of physiological saline (untreated group) or BNP (treated group) starting 5 min before reperfusion and throughout the whole reperfusion. The infarct size, measured by triphenyltetrazolium chloride staining, was reduced by 44% with BNP treatment (P < 0.01). Accordingly, serum levels of creatine kinase and lactate dehydrogenase were markedly reduced in BNP-treated group (P < 0.05) compared with the untreated group. BNP significantly attenuated apoptotic cells (TUNEL-positive cardiomyocyte nuclei) in the myocardium (P < 0.01). The BNP-mediated attenuation of apoptosis was associated with the increased expression of an anti-apoptotic protein Bcl-2 and the reduced expression of a pro-apoptotic protein Bax. Moreover, BNP treatment significantly decreased the magnitude of caspase-3 activation caused by myocardial ischemia-reperfusion. In conclusion, pretreatment with BNP shortly before the onset of reperfusion not only reduces necrosis, but also attenuates myocardial apoptosis. BNP appears to be an ideal pharmacological agent applied as an adjuvant therapy to current myocardial reperfusion strategies.
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PMID:Pretreatment with B-type natriuretic peptide protects the heart from ischemia-reperfusion injury by inhibiting myocardial apoptosis. 1977 27

In this study, transient forebrain ischemia was induced in male Wistar rats with subsequent 3 days of reperfusion (ischemia/reperfusion group) or 2 days of reperfusion followed by 5 min ischemia and another 1 day of reperfusion (postconditioning group) to assess an effect of delayed postconditioning applied two days after a previous lethal ischemic attack. We have examined immunoreactivity of antioxidant enzymes (MnSOD, CuZnSOD) and proteins related to apoptosis development (Bcl-2, Bax). Results of microdensitometric measurements from the vulnerable hippocampal CA1 region and relatively resistant dentate gyrus were compared to sham controls and identically, results of postconditioning group were compared to ischemic one. Our findings show protective effects of postconditioning in both brain regions examined, include increased expression of antioxidant enzymes, mainly CuZnSOD, what can be demonstrated by microdensitometric results: CuZnSOD density after ischemia and reperfusion was 6261.5 +/- 411.35; after postconditioning 9746.6 +/- 584.55. In addition, postconditioning prevents an excessive ischemia-induced increase of pro-apoptotic protein Bax (Bax density after ischemia and reperfusion was 3462.51 +/- 321.66; after postconditioning 1766.89 +/- 255.63).
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PMID:Ischemic postconditioning in the rat hippocampus: mapping of proteins involved in reversal of delayed neuronal death. 2042 51

Studies have demonstrated neuroprotective effects of either TNF-alpha or HSP-70 in ischemia/reperfusion injury following exercise. However, the protective mechanisms involving combined effect of the two proteins, particularly in neuronal apoptosis, remain unclear. This study aims to elucidate the beneficial role of TNF-alpha and HSP-70 in the regulation of apoptotic proteins and ERK signaling in hypoxic injury. Cortical neurons from 20 Sprague-Dawley rat embryos were isolated and cultured in five groups with or without pretreatment with recombinant TNF-alpha, HSP-70 protein or both prior to hypoxic conditions: (1) control; (2) control/hypoxia; (3) TNF-alpha/hypoxia; (4) HSP-70/hypoxia and (5) TNF-alpha/HSP-70/hypoxia. Western blotting was used to detect pro- and anti-apoptotic proteins, including Bax, AIF, Bcl-xL, Bcl-2, and pERK1/2 protein. TNF-alpha and HSP-70 significantly (p<0.05) reduced the levels of pro-apoptotic proteins, Bax and AIF. Also, pretreatment of hypoxic brain tissue with TNF-alpha and HSP-70 significantly (p<0.05) enhanced the levels of anti-apoptotic protein, Bcl-xL. TNF-alpha and HSP-70 together increased Bcl-2 levels by 70%. Hypoxia caused a significant (p<0.05) increase in ERK1/2 phosphorylation levels by 224%. The most effective inhibition of ERK levels was obtained by the combined administration of TNF-alpha and HSP-70. This study suggested that TNF-alpha and HSP-70 together enhance the decrease in pro-apoptotic protein levels and the increase in anti-apoptotic protein levels in the event of neuronal hypoxia through ERK1/2 signal transduction.
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PMID:Combined effect of tumor necrosis factor (TNF)-alpha and heat shock protein (HSP)-70 in reducing apoptotic injury in hypoxia: a cell culture study. 2069 Dec 48

Many toxic factors are generated during stroke that contribute directly to the death of neurons. Several recent studies suggest that a suicide-like phenomena similar to apoptosis or programmed cell death also contributes to the loss of neurons in stroke. The evidence implicating apoptosis in stroke can be divided into three categories; biochemical, molecular and pharmacological. Biochemical evidence: One hallmark of apoptosis is the early activation of destructive enzymes, including endonucleases and proteases. Endonuclease-mediated DNA fragmentation can be observed within 4 h after focal cerebral ischemia and precedes morphological evidence of cell death. Cells with damaged DNA appear to concentrate in the salvageable tissue of the penumbra while necrosis predominates in areas where the sustained lack of blood flow may make tissue salvage impossible. Molecular evidence: Bcl-2 is an anti-apoptotic gene that confers the ability to block apoptosis from a wide variety of stimuli. The levels of bcl-2 can be enhanced by viral gene delivery or transgenic methodology. In cortical tissue where bcl-2 was elevated, neurons were protected from a subsequent ischemic attack. In contrast to bcl-2, p53 is a pro-apoptotic protein. Levels of p53 are elevated after cerebral ischemia and transgenic p53 knockouts exhibit smaller infarcts than wild type control mice. Pharmacological evidence: The process of apoptosis typically involves the activation of enzymes and genes, leading to an irreversible committment to die. Inhibition of new protein synthesis by cycloheximide reduces brain damage after a stroke, suggesting that newly synthesized proteins are contributing to the death of neurons. In addition, inhibition of calpain (an enzyme implicated in certain forms of apoptosis) protects neurons in models of global ischemia, focal ischemia, and hypoxia. In conclusion, the observation that an apoptotic-like process contributes to stroke may have important therapeutic implications since therapies that inhibit apoptosis improve outcome in experimental stroke.
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PMID:Role of apoptosis in acute neurodegenerative disorders. 2155 10

A number of studies have demonstrated that resveratrol (Res), a natural polyphenol compound found in plants, shows potent neuroprotective, anti-inflammatory and antioxidant effects; however, its ability to prevent ischemia-induced brain damage remains unclear. Here we tested whether Res played a neuroprotective role in a rat brain ischemia model induced by middle cerebral artery occlusion (MCAO). Adult male rats were randomly assigned into four experimental groups: sham operation (sham), ischemia treatment (MCAO), Res-treated MCAO (Res+MCAO) and Res alone group (Res+sham). The brain damage size and hippocampal apoptotic neurons in each rat were evaluated by triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) staining, respectively. Long-term potentiation (LTP) induced by high-frequency stimulation (HFS) in the hippocampus was assessed with extracellular recording. The expression of apoptosis-related proteins, i.e., Bcl-2 and Bax, in the hippocampus was detected by western blot. Our results revealed that Res treatment significantly reduced brain infarct volume of MCAO rats as compared to MCAO rats without Res treatment. A significant increase in TUNEL-positive neurons in the hippocampal CA1 region was visualized in the MCAO rats as compared to that of the sham group, but this increase was attenuated with Res treatment. Functionally, extracellular recordings revealed that MCAO operation impaired LTP in the hippocampal CA1 region and the basal synaptic transmission between the Schaffer collaterals, whereas Res treatment rescued the impaired LTP and facilitated synaptic transmission in the CA1 region of the MCAO rats. Res treatment increased the expression of anti-apoptotic protein Bcl-2 and decreased the expression of pro-apoptotic protein Bax in the MCAO rats. The findings suggest that Res can attenuate the deleterious effects of focal cerebral ischemia/reperfusion-induced brain injury and function as a potential neuroprotective agent. The neuroprotective qualities of Res, based on our data, may be attributable to the up-regulation of Bcl-2 expression and down-regulation of Bax expression.
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PMID:Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. 2241 Feb 91


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