Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Kaempferol protects ischemia/reperfusion-induced cardiac damage through the regulation of endoplasmic reticulum stress. 1856 83

In acute thromboembolic stroke, neurological damage is due to ischemia-induced apoptotic death of neuronal cells and the surrounding vascular network. Here, we demonstrate that the BH4 domain of the anti-apoptotic protein, Bcl-x(L), attached to the membrane transport peptide, TAT, reduces stroke injury after intracerebroventricular infusion into immature rats subjected to carotid artery ligation and additional exposure to hypoxia. The injected TAT-BH4 entered neuron bodies, maintained brain architecture, protected neuronal and endothelial cells from apoptosis and promoted neuronal stem cell recruitment. In vitro, TAT-BH4 enhanced the survival of endothelial cells exposed to H(2)O(2), increased neuronal differentiation, and induced axonal remodelling of adult neuronal stem cells. These findings indicate that TAT-BH4 administration protects against acute hypoxia/ischemia injury in the brain by preventing endothelial and neuron cell apoptosis and by inducing neuronal plasticity.
 ...
PMID:Prevention of ischemic brain injury by treatment with the membrane penetrating apoptosis inhibitor, TAT-BH4. 1930 42

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.
 ...
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.
 ...
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.
 ...
PMID:Pretreatment with B-type natriuretic peptide protects the heart from ischemia-reperfusion injury by inhibiting myocardial apoptosis. 1977 27

Diabetes mellitus has been known to mitigate ischemic or pharmacologic preconditioning in ischemia-reperfusion injuries. Remifentanil is a widely used opioid in cardiac anesthesia that possesses a cardioprotective effect against ischemia-reperfusion. We evaluated whether diabetes affected remifentanil preconditioning induced cardioprotection in ischemia-reperfusion rat hearts in view of anti-apoptotic pathways of survival and Ca(2+) homeostasis. Streptozotocin-induced, diabetic rats and age-matched wild-type Sprague-Dawley rats were subjected to a left anterior descending coronary artery occlusion for 30min followed by 1h of reperfusion. Each diabetic and wild-type rat was randomly assigned to the sham, ischemia-reperfusion only, or remifentanil preconditioning group. Myocardial infarct size, activities of ERK1/2, Bcl2, Bax and cytochrome c, and gene expression influencing Ca(2+) homeostasis were assessed. Remifentanil preconditioning significantly reduced myocardial infarct size compared to ischemia-reperfusion only in wild-type rats but not in diabetic rats. Remifentanil preconditioning increased expression of ERK1/2 and anti-apoptotic protein Bcl-2 and decreased expression of pro-apoptotic proteins, Bax and cytochrome c, compared to ischemia-reperfusion only in wild-type rats. In diabetic rat hearts, however, remifentanil preconditioning failed to recover the phosphorylation state of ERK1/2 and to repress apoptotic signaling. In addition, diabetes minimized remifentanil induced modulation of abnormal changes in sarcoplasmic reticulum genes and proteins in ischemia-reperfusion rat hearts. In conclusion, diabetes mitigated remifentanil induced cardioprotection against ischemia-reperfusion, which might be associated with reduced recovery of the activities of proteins involved in anti-apoptotic pathways including ERK1/2 and the abnormal expression of sarcoplasmic reticulum genes as a result of ischemia-reperfusion in rat hearts.
 ...
PMID:Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival. 1994 81

Erythropoietin (EPO) protects the kidneys from ischemia/reperfusion (I/R) injury; however, the exact signalling mechanisms are not fully understood. The serum and glucocorticoid-regulated kinase 1 (SGK1) is an anti-apoptotic protein kinase regulated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway by cellular stimuli, hormones and growth factors. The objective of the present study was to examine the role of SGK1 in the renoprotective effects of EPO in renal I/R injury. In vitro, cultures of HEK293 cells were exposed to 16h hypoxia. Incubation with EPO at a doses of 400U/ml exerted a protective effect on cell death assessed by LDH release and Annexin V FACS analysis. This was paralleled by up-regulation of SGK1 expression, as well as phosphorylation. Downregulation of SGK1 expression by small interfering RNA technique ameliorated the anti-apoptotic effect of EPO treatment. In an in vivo rat model of unilateral renal I/R injury, rats were treated with 500U/kg EPO 24h prior to ischemia. EPO resulted in less severe tissue injury and ameliorated the elevation in creatinine and urea nitrogen levels 24h after reperfusion. Furthermore, SGK1 expression and phosphorylation were higher in EPO compared to vehicle-treated rats as demonstrated by real-time PCR, Western blot and immunofluorescence technique. We conclude that EPO protects from renal I/R injury and SGK1 might contribute to the mediation of EPO effects under ischemic conditions.
 ...
PMID:Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. 1996 32

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.
 ...
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

Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration.
 ...
PMID:Activated protein C protects myocardium via activation of anti-apoptotic pathways of survival in ischemia-reperfused rat heart. 2106 Jul 50

To clarify the relationship between reactive oxygen species (ROS) and cell death during ischemia-reperfusion (I/R), we studied cell death mechanisms in a cellular model of I/R. Oxidant stress during simulated ischemia was detected in the mitochondrial matrix using mito-roGFP, a ratiometric redox sensor, and by Mito-Sox Red oxidation. Reperfusion-induced death was attenuated by over-expression of Mn-superoxide dismutase (Mn-SOD) or mitochondrial phospholipid hydroperoxide glutathione peroxidase (mito-PHGPx), but not by catalase, mitochondria-targeted catalase, or Cu,Zn-SOD. Protection was also conferred by chemically distinct antioxidant compounds, and mito-roGFP oxidation was attenuated by NAC, or by scavenging of residual O(2) during the ischemia (anoxic ischemia). Mitochondrial permeability transition pore (mPTP) oscillation/opening was monitored by real-time imaging of mitochondrial calcein fluorescence. Oxidant stress caused release of calcein to the cytosol during ischemia, a response that was inhibited by chemically diverse antioxidants, anoxia, or over-expression of Mn-SOD or mito-PHGPx. These findings suggest that mitochondrial oxidant stress causes oscillation of the mPTP prior to reperfusion. Cytochrome c release from mitochondria to the cytosol was not detected until after reperfusion, and was inhibited by anoxic ischemia or antioxidant administration during ischemia. Although DNA fragmentation was detected after I/R, no evidence of Bax activation was detected. Over-expression of the anti-apoptotic protein Bcl-X(L) in cardiomyocytes did not confer protection against I/R-induced cell death. Moreover, murine embryonic fibroblasts with genetic depletion of Bax and Bak, or over-expression of Bcl-X(L), failed to show protection against I/R. These findings indicate that mitochondrial ROS during ischemia triggers mPTP activation, mitochondrial depolarization, and cell death during reperfusion through a Bax/Bak-independent cell death pathway. Therefore, mitochondrial apoptosis appears to represent a redundant death pathway in this model of simulated I/R. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection.
 ...
PMID:Mitochondrial oxidant stress triggers cell death in simulated ischemia-reperfusion. 2118 34


<< Previous 1 2 3 4 5 6 7 8 9 Next >>