Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils undergo rapid constitutive apoptosis that is delayed by a range of pathogen- and host-derived inflammatory mediators. We have investigated the ability of the nucleotide ATP, to which neutrophils are exposed both in the circulation and at sites of inflammation, to modulate the lifespan of human neutrophils. We found that physiologically relevant concentrations of ATP cause a concentration-dependent delay of neutrophil apoptosis (assessed by morphology, annexin V/To-Pro3 staining, and mitochondrial membrane permeabilization). We found that even brief exposure to ATP (10 min) was sufficient to cause a long-lasting delay of apoptosis and showed that the effects were not mediated by ATP breakdown to adenosine. The P2 receptor mediating the antiapoptotic actions of ATP was identified using a combination of more selective ATP analogs, receptor expression studies, and study of downstream signaling pathways. Neutrophils were shown to express the P2Y11 receptor and inhibition of P2Y11 signaling using the antagonist NF157 abrogated the ATP-mediated delay of neutrophil apoptosis, as did inhibition of type I cAMP-dependent protein kinases activated downstream of P2Y11, without effects on constitutive apoptosis. Specific targeting of P2Y11 could retain key immune functions of neutrophils but reduce the injurious effects of increased neutrophil longevity during inflammation.
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PMID:Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor. 1805 2

Vanadium, a trace element, as vanadate (VO4(3-)) is known to interfere with a wide variety of enzymes including Ca2+ ATPase and Na+/+ ATPase. VO4(3-) is excreted mainly via the kidney. In renal insufficiency, the impaired VO4(3-) excretion leads to VO4(3-) accumulation in blood.The present study explored the effect of VO4(3-) on eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared from circulating blood. Stimulators of eryptosis include an increase of the cytosolic Ca2+ concentration. Erythrocyte Ca2+ activity was estimated from Fluo-3 fluorescence, phosphatidylserine exposure from annexin V-binding, and erythrocyte volume from forward scatter in FACS analysis. Exposure of erythrocytes to VO4(3-) increased cytosolic Ca2+ concentration, enhanced the percentage of annexin V-binding erythrocytes, decreased erythrocyte forward scatter, and lowered the intracellular ATP concentration. In conclusion, VO4(3-) induces eryptosis at least partially through increase of cytosolic Ca2+ concentration, an effect presumably contributing to the development of anemia in chronic renal failure.
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PMID:Vanadate-induced suicidal erythrocyte death. 1831 5

A series of novel thiobenzanilides is described. These compounds have been previously found to show strong biological activity such as antimycotic and antifungal actions. This is the first demonstration on the mechanism of the anticancer effect of thiobenzanilide agents (4a-c) on human melanoma A375 cells. The cytotoxic studies of compounds 4a-c on human melanoma A375 cells indicate thiobenzanilides induced higher cytotoxicity than nitrobenzanilides (3a-c). In addition, DNA flow cytometric analysis shows that 4a-c displays a significant G2/M phase arrest, which progresses to early apoptosis as detected by flow cytometry after double-staining with annexin V and propidium iodide (PI). Because cellular apoptosis is often preceded by the disruption of mitochondrial function, the assessment of mitochondrial function in 4a-c-treated cells is worthy of investigation. Our data revealed that treatment of A375 cells with 4a-c resulted in the loss of mitochondrial membrane potential (DeltaPsi(mt)), a reduction of ATP synthesis, increased reactive oxygen species (ROS) generation, and activation of caspase-3. Thus, we suggest that 4a-c agents are potent inducers of cell apoptosis in A375 cells.
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PMID:Synthesis and biological evaluation of thiobenzanilides as anticancer agents. 1835 35

For islet transplantation, it is important to obtain an available islet mass adequate for diabetes reversal from a single donor pancreas. A recent report demonstrated that the use of M-Kyoto solution instead of UW solution improved islet yields in the two-layer method for pancreas preservation. The present study investigated whether the ductal injection of a large volume of preservation solution (UW and M-Kyoto solution) before pancreas storage improves islet yields. Islet yield both before and after purification was significantly higher in the ductal injection (+) group compared with the ductal injection (-) group. TUNEL-positive cells in the ductal injection (+) group were significantly decreased in comparison to the ductal injection (-) group. The ductal injection of preservation solution increased the ATP level in the pancreas tissue and reduced trypsin activity during the digestion step. Annexin V and PI assays showed that the ductal injection prevents islet apoptosis. In a transplant model, the ductal injection improved islet graft function. These findings suggest that the ductal injection of preservation solution, especially the M-Kyoto solution, leads to improved outcomes for pancreatic islet transplantation. Based on these data, this technique is now used for clinical islet transplantation from non-heart-beating donor pancreata or living donor pancreas.
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PMID:Ductal injection of preservation solution increases islet yields in islet isolation and improves islet graft function. 1846 37

Cisplatin, a cytotoxic drug for the treatment of cancer, induces suicidal death or apoptosis of nucleated cells. Side effects of cisplatin include anemia, which, at least in theory, could similarly result from suicidal cell death. Erythrocyte suicidal death or eryptosis is characterized by cell shrinkage and cell membrane scrambling, the latter leading to exposure of phosphatidylserine (PS) at the cell surface. PS-exposing cells are rapidly cleared from circulating blood. The present experiments explored whether cisplatin could trigger eryptosis. According to forward scatter in FACS analysis, a 48 h exposure to cisplatin (> or =1 microM) indeed decreased cell volume and, according to annexin V-binding, cisplatin (> or =1 microM, 48 h) indeed increased PS exposure at the cell surface. Cisplatin did not induce hemolysis. According to Fluo3 fluorescence, cisplatin increased cytosolic Ca2+ activity, a known stimulator of eryptosis. In the absence of extracellular Ca2+, the effect of cisplatin on annexin V-binding was blunted. Cisplatin did not significantly modify the formation of ceramide, another stimulator of eryptosis. Cisplatin moderately decreased the cellular concentration of ATP, which is known to favour eryptosis. In conclusion, cisplatin triggers suicidal erythrocyte death at least partially by increasing cytosolic Ca2+ activity. The effect contributes to or even accounts for the development of anemia during cisplatin treatment.
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PMID:Suicidal erythrocyte death triggered by cisplatin. 1849 24

The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1beta) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1beta as a modulating and chondrocyte apoptosis inducing agent. Different doses of HA (10, 20, and 40 microg/mL) were added 1 h prior to the addition of IL-1beta to a monolayer culture of freshly isolated juvenile rat chondrocytes. The ratio of apoptotic cell death was surveyed by Annexin V-FITC and propidium iodide double-labeling FACS analysis. The mitochondrial membrane potential of chondrocytes was evaluated by rhodamine-123 fluorescence. The mitochondrial function was evaluated through detecting the ATP production by a luciferase assay. The reverse transcription polymerase chain reaction (RT-PCR) was performed to measure mRNA expression levels of inducible oxide synthase (iNOS). HA could inhibit IL-1beta-induced chondrocyte apoptosis in our cell culture model system. It was showed that addition of HA to the medium was able in a dose-dependent way to reduce the impairment of the mitochondrial membrane potential and to restore mitochondrial ATP production. This study shows that HA could suppress in a dose-dependent way chondrocyte apoptosis in our IL-1beta-induced osteoarthritis model. The suppression of inflammatory cytokine activity within the joint might be one important mechanism of the clinical action of intraarticular injection of HA in the treatment of OA.
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PMID:The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis. 1852 10

Neutrophils represent the most common granulocyte subtype present in blood. The short half-life of circulating neutrophils is regulated by spontaneous apoptosis, and tissue infiltrating neutrophils die by apoptosis and secondary necrosis. The mechanism of neutrophil apoptosis has been the subject of many studies; however, the mechanism of neutrophil secondary necrosis is less clear. Human cathelicidin cationic peptide 18, proteolytically processed to its active form, LL-37, is secreted by neutrophils and epithelial cells and shown to have effects in addition to bacterial lysis. We demonstrate here that LL-37 affects neutrophil lifespan by the pathway of secondary necrosis, rapidly converting annexin V-positive (AV(+)), propidium iodide-negative (PI(-); apoptotic) cells into PI(+) (necrotic) cells with the release of IL-8, IL-1R antagonist, ATP, and intact granules. The effects of LL-37 on apoptotic neutrophils are neither energy-dependent nor affected by pretreatment with G-CSF, GM-CSF, TNF-alpha, and LPS and are partially inhibited by human serum. Moreover, LL-37 decreases CXCR2 expression of AV(-)PI(-) (live) neutrophils, suggesting an effect on the neutrophil response to its chemotactic factors, including IL-8. Thus, the lifespan and inflammatory functions of neutrophils are directly affected by LL-37.
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PMID:Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin. 1852 73

Environmental exposure to arsenic has been associated with anemia, which could result from suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and phosphatidylserine exposure at the erythrocyte surface. Eryptosis is triggered by increase in cytosolic Ca2+ concentration, ceramide and energy depletion. The present experiments explored, whether arsenic stimulates eryptosis. According to annexin V-binding, arsenic trioxide (7 microM) within 48 h significantly increased phosphatidylserine exposure of human erythrocytes without inducing hemolysis. According to forward scatter, arsenic trioxide (7 microM) significantly decreased cell volume. Moreover, Fluo3-fluorescence showed that arsenic (10 microM) significantly increased cytosolic Ca2+ concentration. According to binding of respective fluorescent antibodies, arsenic trioxide (10 microM) significantly increased ceramide formation. Arsenic (10 microM) further lowered the intracellular ATP concentration. Removal of extracellular Ca2+ or inhibition of the Ca2+-permeable cation channels with amiloride blunted the effects of arsenic on annexin V-binding and cell shrinkage. In conclusion, arsenic triggers suicidal erythrocyte death by increasing cytosolic Ca2+ concentration, by stimulating the formation of ceramide and by decreasing ATP availability.
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PMID:Arsenic-induced suicidal erythrocyte death. 1863 41

Peptidoglycans (PGNs) from bacterial cell walls belong to 'pathogen-associated molecular patterns' (PAMP), which modify the course of an infection with bacterial pathogens. Bacterial infections may lead to anaemia, which at least partially could result from accelerated erythrocyte death. The present study explored the effect of PGNs on eryptosis, a stress-induced suicidal death of erythrocytes, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared from circulating blood. Eryptosis is triggered by an increase in the cytosolic Ca(2+) concentration and by formation of ceramide. Erythrocyte Ca(2+) activity was estimated from Fluo3 fluorescence, ceramide formation by fluorescent antibodies, phosphatidylserine exposure from annexin V-binding, and erythrocyte volume from forward scatter in fluorescence activated cell sorting (FACS) analysis. Exposure of erythrocytes to PGNs increased cytosolic Ca(2+) concentration, increased ceramide formation, enhanced the percentage of annexin V-binding erythrocytes, decreased erythrocyte forward scatter, and lowered the intracellular ATP concentration. The effect of peptidoglycans was significantly blunted in the absence of extracellular Ca(2+). The clearance of erythrocytes exposed to PGNs was significantly enhanced in vivo. In conclusion, peptidoglycans induce eryptosis at least partially through an increase in the cytosolic Ca(2+) concentration, an effect presumably contributing to the development of anaemia during bacterial infections.
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PMID:Effect of peptidoglycans on erythrocyte survival. 1867 99

The effect of target-directed regulation of the uncoupling protein-2 (UCP-2) gene expression on the ischemia-reperfusion injury of hepatocytes under different conditions was investigated. The expression plasmid and RNAi plasmid targeting UCP-2 gene were constructed and transfected into normal hepatocytes and fatty liver cells, respectively. The expression of UCP-2 mRNA was detected by real time PCR. The cells were divided into normal cell group (NCG), group of normal cells transfected with empty vector (EVNCG), group of normal cells transfected with expression plasmid (EPNCG), fatty liver cell group (FCG) and group of fatty liver cells transfected with RNAi plasmid (RPFCG). The ischemia-reperfusion model in vitro was established. One, 6, 12 and 24 h after reperfusion, Annexin V/PI flow cytometry was used to measure cell necrosis rate, apoptosis rate and survival rate. Simultaneously, the intracellular ATP, ROS and MDA levels were determined. The results showed that 1, 6, 12 and 24 h after ischemia-reperfusion, the intracellular ROS, MDA and ATP levels and cell survival rate in EPNCG were significantly lower, and cell necrosis rate significantly higher than in NCG and EVNCG, but there was no significant difference in apoptosis rate among NCG, EVNCG and EPNCG (P>005). Six, 12 and 24 h after reperfusion there was no significant difference in ROS, MDA levels and apoptosis rate between FCG and RPFCG (P>0.05), but the ATP level and survival rate of cells in RPFCG were higher than in FCG (P<0.05). It was concluded that down-regulation of the UCP-2 gene expression in steatotic hepatocytes could alleviate the ischemia-reperfusion injury of liver cells.
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PMID:Effect of target-directed regulation of uncoupling protein-2 gene expression on ischemia-reperfusion injury of hepatocytes. 1884 38


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