UNIPROT:P08758 - FACTA Search

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Query: UNIPROT:P08758 (annexin V)
9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neural progenitor cells (NPCs) have the potential to survive brain ischemia and participate in neurogenesis after stroke. However, it is not clear how survival responses are initiated in NPCs. Using embryonic mouse NPCs and the in vitro oxygen and glucose deprivation (OGD) model, we found that angiopoietin-1 (Ang1) could prevent NPCs from OGD-induced apoptosis, as evidenced by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and annexin V labeling. Ang1 significantly elevated tunica intima endothelial kinase 2 (Tie2) autophosphorylation level, suggesting the existence of functional Tie2 receptors on NPCs. NPCs under OGD conditions exhibited reduction of Akt phosphorylation, decrease of the Bcl-2/Bax ratio, activation of caspase-3, cleavage of PARP, and downregulation of beta-catenin and nestin. Ang1 reversed the above changes concomitantly with significant rising of survival rates of NPCs under OGD, but all these effects of Ang1 could be blocked by either soluble extracellular domain of Tie2 Fc fusion protein (sTie2Fc) or the phosphoinositide 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one (LY294002). Our findings suggest the existence of an Ang1-Tie2-PI3K signaling axis that is essential in initiation of survival responses in NPCs against cerebral ischemia and hypoxia.
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PMID:An Ang1-Tie2-PI3K axis in neural progenitor cells initiates survival responses against oxygen and glucose deprivation. 1940 99

Application of volatile anesthetics during the onset of reperfusion reduced ischemia-induced cardiac and brain injury (anesthetic postconditioning). This study was designed to evaluate whether volatile anesthetics induced a postconditioning effect in endothelial cells. Bovine pulmonary arterial endothelial cell (BPAEC) cultures were exposed to oxygen-glucose deprivation, a condition to simulate ischemia in vitro, for 3 h. The volatile anesthetics isoflurane and desflurane were applied during the early phase of simulated reperfusion. Cell injury was quantified by lactate dehydrogenase (LDH) release and flow cytometrical measurement after annexin V and propidium iodide staining. Oxygen-glucose deprivation and the subsequent simulated reperfusion increased LDH release and annexin V-positive staining cells, a characteristic of cell apoptosis. Posttreatment with isoflurane, but not desflurane, reduced this cell injury. This protection was apparent even when 2% isoflurane was applied at 60 min after the onset of reperfusion. The isoflurane postconditioning effect was abolished by glybenclamide, a general ATP sensitive K(+) (K(ATP)) channel blocker, 5-hydroxydecanoate, a mitochondrial K(ATP) channel blocker, and chelerythrine, a protein kinase C inhibitor. Diazoxide, a mitochondrial K(ATP) channel activator, applied at the onset of reperfusion also decreased oxygen-glucose deprivation-induced endothelial cell injury. This diazoxide-induced protection was abolished by chelerythrine and 5-hydroxydecanoate. We conclude that isoflurane induced a postconditioning effect in BPAEC. The effective time window of isoflurane postconditioning was from 0 to 60 min after the onset of reperfusion. This isoflurane postconditioning effect may be mediated by mitochondrial K(ATP) channels and PKC. PKC may be downstream of mitochondrial K(ATP) channels for this isoflurane effect.
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PMID:Isoflurane induces a postconditioning effect on bovine pulmonary arterial endothelial cells exposed to oxygen-glucose deprivation. 1946 84

This study was designed to determine whether FPS-1, the water-soluble polysaccharide isolated from fuzi, protected against hepatic damage in hepatic ischemia-reperfusion injury in rats, and its mechanism. SD rats were subjected to 60 min of hepatic ischemia, followed by 120 min reperfusion. FPS-1 (160 mg/kg/day) was administered orally for 5 days before ischemia-reperfusion injury in treatment group. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were assayed to evaluate liver functions. Liver samples were taken for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), that catalase (CAT) in liver. Na(+)-K(+)-ATPase and Ca(2+)-ATPase in mitochondria were measured with colorimetry method. Morphological changes were also investigated by using both light microscopy and electron microscopy (EM). In addition, apoptosis and oncosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. Serum AST and ALT levels were elevated in groups exposed to ischemia-reperfusion (p < 0.05). Ischemia-reperfusion caused a marked increase in MDA level, and significant decreases in hepatic SOD and CAT (p < 0.05). Na(+)-K(+)-ATPase and Ca(2+)-ATPase were reduced in ischemia-reperfusion groups compared to the sham group (p < 0.05). Oncosis and apoptosis were also observed in ischemia-reperfusion groups. Pretreatment with FPS-1 reversed all these biochemical parameters as well as histological alterations, evidently by increased SOD, CAT, reduced MDA and histological scores compared to the model group (p < 0.05). FPS-1 could attenuate the necrotic states by the detection of immunofluorescent flow cytometry analysis. Pretreatment with FPS-1 reduced hepatic ischemia-reperfusion injury through its potent antioxidative effects and attenuation of necrotic states.
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PMID:Study on pretreatment of FPS-1 in rats with hepatic ischemia-reperfusion injury. 1950 75

Animal studies have shown that previous exposure to lipopolysaccharide (LPS) can limit ischemia-reperfusion injury. We tested whether pretreatment with LPS also protects against ischemia-reperfusion injury in humans in vivo. Fourteen volunteers received bolus injections of incremental dosages of LPS on 5 consecutive days (LPS group). Before the first and 1 day after the last LPS administration, the forearm circulation of the non-dominant arm was occluded for 10 min, with concomitant intermittent handgripping to induce transient ischemia. After reperfusion, 0.1 mg of ( 99m)Tc-labeled annexin A5 (400 MBq) was injected intravenously to detect phosphatidylserine expression as an early marker of ischemia-reperfusion injury. Similarly, the control group (n = 10) underwent the ischemic exercise twice, but without pretreatment with LPS. Annexin A5 targeting was expressed as the percentage difference in radioactivity in the thenar muscle between both hands. Endotoxin tolerance developed during 5 consecutive days of LPS administration. Annexin A5 targeting was 12.1 +/- 2.2% and 10.4 +/- 2.1% before LPS treatment at 1 h and 4 h after reperfusion, compared to 12.2 +/- 2.4% and 8.9 +/- 2.1% at 1 h and 4 h after reperfusion on day 5 (P = 1.0 and 0.6, respectively). Also, no significant changes in annexin A5 targeting were found in the control group. So, in this model, LPS-tolerance does not protect against ischemia-reperfusion injury in humans in vivo.
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PMID:Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo. 1971 89

Molecular and cellular imaging of atherosclerosis has garnered more interest at the beginning of the 21st century, with aims to image in vivo biological properties of plaque lesions. Apoptosis seems an attractive target for the diagnosis of vulnerable atherosclerotic plaques prone to a thrombotic event. The aim of the present work was to screen for apoptosis peptide binders by phage display with the final purpose to detect apoptotic cells in atherosclerotic plaques by magnetic resonance imaging (MRI). A phosphatidylserine-specific peptide identified by phage display was thus used to design an MRI contrast agent (CA), which was evaluated as a potential in vivo reporter of apoptotic cells. A library of linear 6-mer random peptides was screened in vitro against immobilized phosphatidylserine. Phage DNA was isolated and sequenced, and the affinity of peptides for phosphatidylserine was evaluated by enzyme-linked immunosorbent assay. The phosphatidylserine-specific peptide and its scrambled homologue were attached to a linker and conjugated to DTPA-isothiocyanate. The products were purified by dialysis and by column chromatography and complexed with gadolinium chloride. After their evaluation using apoptotic cells and a mouse model of liver apoptosis, the phosphatidylserine-targeted CA was used to image atherosclerotic lesions on ApoE(-/-) transgenic mice. Apoptotic cells were detected on liver and aorta specimens by the immunostaining of phosphatidylserine and of active caspase-3. Sequencing of the phage genome highlighted nine different peptides. Their alignment with amino acid sequences of relevant proteins revealed a frequent homology with Ca2+ channels, reminiscent of the function of annexins. Alignment with molecules involved in apoptosis provides a direct correlation between peptide selection and utility. The in vivo MRI studies performed at 4.7 T provide proof of concept that apoptosis-related pathologies could be diagnosed by MRI with a low molecular weight paramagnetic agent. The new CA could have real potential in the diagnosis and therapy monitoring of atherosclerotic disease and of other apoptosis-associated pathologies, such as cancer, ischemia, chronic inflammation, autoimmune disorders, transplant rejection, neurodegenerative disorders, and diabetes mellitus. The phage display-derived peptide could also play a potential therapeutic role through anticoagulant activity by mimicking the role of annexin V, the endogenous ligand of phosphatidylserine.
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PMID:Peptidic targeting of phosphatidylserine for the MRI detection of apoptosis in atherosclerotic plaques. 1974 79

Ischemia-reperfusion injury (IRI) is a common and serious complication of reperfusion following vascular occlusion. We present a novel interpretation of the pathogenesis of IRI. According to this hypothesis, anoxia resulting from ischemia allows translocation of phosphatidylserine to the surface of endothelial cells (ECs), providing an attachment site for leukocytes and platelets. This attachment impedes blood flow through the microvasculature. During IRI mediators of increased vascular permeability are produced, resulting in edema. We have developed a recombinant homodimer of human Annexin V, Diannexin, to attenuate IRI. Annexin V (36 kDa) rapidly passes from the circulation into the urine. In Diannexin 2 annexin V molecules are joined by a short peptide linker to produce a 73 kDa protein, which exceeds the renal filtration threshold. Diannexin has a half-life of about 2.5 hours in the human circulation. Diannexin also has a higher affinity for phosphatidylserine on cell surfaces than the monomer has. Such binding inhibits leukocyte attachment to ECs, and inflammatory mediator formation, during IRI. The aim of the study now reported was to ascertain the effects of Diannexin on IRI in the rat cremaster muscle flap, as revealed by intravital microscopy. During IRI there was increased attachment of leukocytes to ECs, reduced blood flow and augmented vascular permeability. Administration of Diannexin before or just after ischemia prevented these effects. Diannexin inhibited transmigration of leukocytes during IRI. Edema complicates peripheral vascular surgery, stroke, and other clinical conditions. Diannexin has proven to be safe when administered to patients after major surgical operations, and it may be useful to prevent IRI associated with peripheral vascular surgery.
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PMID:Diannexin treatment decreases ischemia-reperfusion injury at the endothelial cell level of the microvascular bed in muscle flaps. 1980 47

In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.
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PMID:4-Guanidino-n-butyl syringate (Leonurine, SCM 198) protects H9c2 rat ventricular cells from hypoxia-induced apoptosis. 1994 Jun 42

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.
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PMID:Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. 1996 32

Regulator of G protein signaling (RGS) family members, such as RGS2, interact with Galpha subunits of heterotrimeric G proteins, accelerating the rate of GTP hydrolysis and attenuating the intracellular signaling triggered by the G protein-coupled receptor-ligand interaction. They are also reported to regulate G protein-effector interactions and form multiprotein signaling complexes. Ischemic stress-induced changes in RGS2 expression have been described in astrocytes, and these changes are associated with intracellular signaling cascades, suggesting that RGS2 upregulation may be an important mechanism by which astrocytes may regulate RGS2 function in response to physiological stress. However, information on the functional roles of stress-induced modulation of RGS2 protein expression in astrocyte function is limited. We report the role of ischemic stress in RGS2 protein expression in rat C6 astrocytoma cells and primary mouse astrocytes. A marked increase in RGS2 occurred after ischemic stress induced by chemicals (sodium azide and 2-deoxyglucose) or oxygen-glucose deprivation (OGD, real ischemia). RGS2 mRNA expression was markedly enhanced by 1 h of exposure to chemical ischemia or 6 h of OGD followed by 2 or 6 h of recovery, respectively. This enhanced expression in primary astrocytes and C6 cells was restored to baseline levels after 12 h of recovery from chemically induced ischemic stress or 4-6 h of recovery from OGD. RGS2 protein was also significantly expressed at 12-24 h of recovery from ischemic insult. Ischemia-induced RGS2 upregulation was associated with enhanced apoptosis. It significantly increased annexin V-positive cells, cleaved caspase-3, and enhanced DNA ladder formation and cell cycle arrest. However, a small interfering RNA (siRNA)-mediated RGS2 knockdown reversed the apoptotic cell death associated with ischemia-induced RGS2 upregulation. Upregulated RGS2 was significantly inhibited by SB-203580, a p38 MAPK inhibitor. Rottlerin, a potent inhibitor of PKCdelta, completely abrogated the increased RGS2 expression. We also examine whether ischemia-induced RGS2-mediated apoptosis is affected by siRNA-targeted endogenous PKCdelta downregulation or its phosphorylation. Although RGS2 upregulation was not affected, siRNA transfection significantly suppressed endogenous PKCdelta mRNA and protein expressions. Ischemia-induced PKCdelta phosphorylation and caspase-3 cleavage were dose dependently inhibited by PKCdelta knockdown, and this endogenous PKCdelta suppression reversed ischemia-induced annexin V-positive cells. This study suggests that ischemic stress increases RGS2 expression and that this condition contributes to enhanced apoptosis in C6 cells and primary astrocytes. The signaling it follows may involve PKCdelta and p38 MAPK pathways.
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PMID:Ischemia induces regulator of G protein signaling 2 (RGS2) protein upregulation and enhances apoptosis in astrocytes. 2003 8

The effects of a small interfering RNA targeting ryanodine receptor 2 (si-Ryr2) on cardiomyocytes injury following a simulated ischemia-reperfusion (I/R) were investigated. Pretreated with si-Ryr2 or ryanodine, primary cultures of neonatal rat cardiomyocytes were subjected to a protocol of simulated I/R. Compared with control, the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and the generation of reactive oxygen species (ROS) was significantly augmented after I/R. Concomitant with these, cell injury assessed by Annexin V/PI staing, mitochondria membrane potential (DeltaPsim) and the leakage of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were aggravated. Si-Ryr2 treatment reduced [Ca(2+)](i) and ROS generation and protected the cardiomyocytes from subsequent I/R injury, as evidenced by stable DeltaPsim and decreased Annexin V(+) PI(-) staing and enzymes release. Moreover, si-Ryr2 exerted more effective protection on I/R injury compared to ryanodine. The present study demonstrated for the first time that in neonatal cardiomyocytes, si-Ryr2 reduces cell death associated with attenuating [Ca(2+)](i) and ROS production. Furthermore, we attempt to speculate that si-Ryr2 excel ryanodine in Ryr2 function research of cardioprotection.
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PMID:RNAi targeting ryanodine receptor 2 protects rat cardiomyocytes from injury caused by simulated ischemia-reperfusion. 2005 23

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