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

Placental apoptosis is increased in vivo in preeclampsia (PE) and intrauterine growth restriction (IUGR). The cause and pathological implications of this phenomenon are unknown. This study considers the apoptotic susceptibility of villous trophoblasts from normal, PE, and IUGR pregnancies. Cultured cytotrophoblasts (CTs) and an in vitro model of syncytialization were used. CTs were isolated from term placentas of 12 normal, 12 PE, and 12 IUGR pregnancies. Apoptosis was determined by terminal dUTP nick-end labeling (TUNEL), Annexin V binding, and ADP:ATP ratios. Cells were stimulated with tumor necrosis factor-alpha/interferon-gamma or reduced oxygen (<5 KPa). For CTs, ADP:ATP <1 correlates with Annexin V binding. For normal pregnancy, tumor necrosis factor-alpha and depleted oxygen significantly increased TUNEL, Annexin V binding and ADP:ATP in CTs and syncytiotrophoblasts (STs). Spontaneous apoptosis was similar between groups for both cell types. After stimulation, TUNEL and Annexin V binding of CTs were significantly raised in PE and IUGR as compared with normal pregnancy. After oxygen reduction, ADP:ATP in CTs and STs were significantly elevated in IUGR. TUNEL was also increased in STs in PE after oxygen depletion and was significantly raised in STs from IUGR pregnancies after stimulation with both agonists. This is the first description of enhanced apoptosis in isolated villous trophoblasts in PE and IUGR. These intrinsic differences may represent an important factor in the pathophysiology of these conditions.
 ...
PMID:Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. 1254 21

Although mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels have been reported to reduce the extent of apoptosis, the critical timing of mitoK(ATP) channel opening required to protect myocytes against apoptosis remains unclear. In the present study, we examined whether the mitoK(ATP) channel serves as a trigger of cardioprotection against apoptosis induced by oxidative stress. Apoptosis of cultured neonatal rat cardiomyocytes was determined by flow cytometry (light scatter and propidium iodide/annexin V-FITC fluorescence) and by nuclear staining with Hoechst 33342. Mitochondrial membrane potential (DeltaPsi) was measured by flow cytometry of cells stained with rhodamine-123 (Rh-123). Exposure to H(2)O(2) (500 microM) induced apoptosis, and the percentage of apoptotic cells increased progressively and peaked at 2 h. This H(2)O(2)-induced apoptosis was associated with the loss of DeltaPsi, and the time course of decrease in Rh-123 fluorescence paralleled that of apoptosis. Pretreatment of cardiomyocytes with diazoxide (100 microM), a putative mitoK(ATP) channel opener, for 30 min before exposure to H(2)O(2) elicited transient and mild depolarization of DeltaPsi and consequently suppressed both apoptosis and DeltaPsi loss after 2-h exposure to H(2)O(2). These protective effects of diazoxide were abrogated by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 microM) but not by the sarcolemmal K(ATP) channel blocker HMR-1098 (30 microM). Our results suggest for the first time that diazoxide-induced opening of mitoK(ATP) channels triggers cardioprotection against apoptosis induced by oxidative stress in rat cardiomyocytes.
 ...
PMID:Diazoxide triggers cardioprotection against apoptosis induced by oxidative stress. 1262 83

Infectivity of Leishmania promastigotes has been shown to be growth cycle-dependent and restricted to the stationary phase. By using annexin V-FITC binding and procoagulant activity measurement assays, we show here that the promastigotes in the stationary phase contain significantly higher amounts of phosphatidylserine (PS) on their surface as compared to the log phase promastigotes. We also demonstrate that the infectivity of the promastigotes is determined by the presence of PS on their surface. In addition, by using NBD-labelled phospholipids, we show that the promastigote plasma membrane contains ATP-dependent out-to-in and ATP-independent in-to-out PS translocases which regulate the PS localisation in two-halves of the membrane bilayer, and that the greater amounts of external PS observed in the stationary phase promastigotes is perhaps due to the slower ATP-dependent out-to-in PS movements in these cells, as compared to the log phase promastigotes.
 ...
PMID:Transbilayer translocation of membrane phosphatidylserine and its role in macrophage invasion in Leishmania promastigotes. 1270 91

Acute renal failure is a dose-limiting factor during cisplatin chemotherapy. We have previously shown in rats that the hydroxyl radical scavenger edaravone reverses cisplatin-induced in vivo renal damage. In the present study, the role of poly(ADP-ribose) polymerase (PARP) in cisplatin nephrotoxicity was investigated in porcine tubular cells LLC-PK1. Cell injury was elicited by transient exposure to 500 microM cisplatin for 1 h or continuous exposure to 30 microM cisplatin for 24 h. Various hydroxyl radical scavengers reversed cell damage in a transient but not permanent model. The cell injury seemed to be necrosis and apoptosis in transient and permanent models, respectively, as assessed by TUNEL method and Annexin V stain. PARP inhibitors such as 3-aminobenzamide and benzamide inhibited cell damage in transient but not permanent model. PARP-dependent cell injury was also observed after transient exposure to hydroxyl radical-generating solution. We demonstrated for the first time the activation of PARP in renal tubular cells by transient cisplatin exposure, as determined by immunofluorescent stain with anti-poly(ADP-ribose) antibody. Moreover, ATP was depleted by transient exposure to cisplatin or hydroxyl radical, both of which were reversed by PARP inhibitors. These findings suggest that hydroxyl radical generation followed by PARP activation contributes to the necrotic cell injury caused by a transient exposure to cisplatin.
 ...
PMID:Role of poly(ADP-ribose)polymerase in cisplatin-induced injury in LLC-PK1 cells. 1455 61

G3139 is an 18-mer phosphorothioate oligodeoxyribonucleotide, which is targeted to the initiation codon region of the bcl-2mRNA. Although treatment of PC3 prostate cancer cells with G3139, which contains two CpG motifs, causes a dramatic decrease in bcl-2 protein expression after 3 days, it did not result in significant cellular apoptosis, as it does in many other cell lines. The absence of apoptosis was demonstrated by the absence of pro-caspase 3 cleavage products and of Annexin V cell surface expression. In addition, ATP production and the mitochondrial membrane potential DeltaPsim were preserved. Despite this, G3139 significantly inhibited the rate of cellular proliferation in complete media and blocked cloning in soft agar. G4232, a variant of G3139 that down-regulates bcl-2 expression to the same extent but has both CpG cytidines C5 methylated, was only minimally antiproliferative. A series of mismatched G3139-related oligomers were synthesized that could also substantially down-regulate bcl-2 protein expression, but only if the CpG motifs were preserved, demonstrating the presence of additional non-antisense mechanisms. G3139 caused production of reactive oxygen species in growth-arrested cells and oxidation of nuclear guanosine to 8-hydroxy-2'-deoxyguanosine, as determined by 1F7 monoclonal antibody staining. Bromodeoxyuridine incorporation studies demonstrated that G3139 induced a G1-S entry block and an intra-S-phase block in PC3 cells that persisted as long as 3 days. This finding coincides with the observation that expression of several proteins encoded by S-phase genes, including c-myb and poly(ADP-ribose) polymerase, were significantly reduced. These results illustrate the complexity of the mechanism of action of G3139 in PC3 cells.
 ...
PMID:G3139 (oblimersen) may inhibit prostate cancer cell growth in a partially bis-CpG-dependent non-antisense manner. 1457 68

We have shown previously that flow-adapted endothelial cells respond to cessation of flow with cell membrane depolarization and increased production of reactive oxygen species, resulting in activation of transcription factors and increased DNA synthesis. This study utilized flow cytometry to evaluate cellular proliferation with ischemia and to determine the role of reactive oxygen species and apoptosis. PKH26-labeled rat pulmonary microvascular endothelial cells were seeded in an artificial capillary system and subjected to flow at 5 dynes/cm(2) for 96 h or for 72 h followed by 24 h of simulated "ischemia." Ischemia resulted in a 2.5-fold increase in the cellular proliferation index. Cell-cycle analysis showed G0/G1 arrest and decreased S plus G2/M during flow adaptation, whereas ischemia resulted in a three-fold increase of cells in S plus G2/M phases. Apoptotic cells as detected by TUNEL and annexin V binding assays were ~5% of total cells with no differences between static, flow-adapted, and "ischemic" groups. Reactive oxygen species production during a 1-h period following onset of ischemia was confirmed by oxidation of the fluorophore, dichlorofluorescein, and was inhibited by cromakalim, a K(ATP) channel agonist, or diphenyleneiodonium, a flavoprotein inhibitor. Cromakalim and diphenyleneiodonium also markedly inhibited cell proliferation in the flow-adapted ischemic cells, but had no effect on subconfluent cells cultured under static conditions. These results indicate reactive oxygen species-dependent endothelial cell proliferation in flow-adapted microvascular endothelial cells as a response to ischemia and indicate that this response is not a consequence of apoptosis.
 ...
PMID:Endothelial cell proliferation associated with abrupt reduction in shear stress is dependent on reactive oxygen species. 1502 26

Treatment of mouse macrophages with picolinic acid (PA) and gamma-interferon (IFNgamma) led to the restriction of Mycobacterium avium proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or H(2)O(2) failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. N-Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome-endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFNgamma depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.
 ...
PMID:Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage activation and apoptosis induction by picolinic acid plus IFNgamma. 1513 12

Inflammatory mechanisms are critical in the arterial response to injury. Both IL-1 and the naturally occurring inhibitor of IL-1, IL-1R antagonist (IL-1ra), are expressed in the arterial wall, and in particular in the endothelium. Previous studies suggest that endothelial cells only make the intracellular type I isoform of IL-1ra (icIL-1ra1), an isoform known to lack a secretory signal peptide. It is unclear how icIL-1ra is released from the endothelial cell to act as an antagonist on cell surface IL-1 type I receptors. IL-1beta, which also lacks a secretory signal peptide, may be released by ATP stimulation of the P2X(7)R. Therefore, we examined whether icIL-1ra1 release occurs in an analogous manner, using both the mouse macrophage cell line RAW264.7 and HUVECs. P2X(7)R activation caused icIL-1ra1 release from LPS-primed RAW264.7 macrophages and from HUVECs. This release was inhibited in the absence of extracellular calcium, and attenuated by preincubation with oxidized ATP, KN62, and apyrase. Endogenous ATP release, which also facilitated release of icIL-1ra1, was detected during LPS treatment of both RAW264.7 macrophages and HUVECs. Annexin V assays showed that ATP stimulation resulted in a rapid phosphatidylserine (PS) exposure on the cell surface of RAW264.7 macrophages, and that PS-exposed microvesicles contained icIL-1ra1. However, PS flip and microvesicle shedding was not apparent in ATP-treated HUVECs. These data support a general role for the P2X(7)R in the release of leaderless cytokines into the extracellular medium, and indicate how icIL-1ra1 may act upon its extracellular target, the IL-1R.
 ...
PMID:Secretion of intracellular IL-1 receptor antagonist (type 1) is dependent on P2X7 receptor activation. 1524 Jul 11

Caveolae appear in a multitude of processes encompassing growth regulation and trafficking. We demonstrate the abundant presence of ESA/reggie-1/flotillin-2, ATP synthase beta subunit and annexin V in endothelial caveolae by immunopurification of caveolae from vascular endothelial membrane. Five proteins are abundant in a caveolin-1 protein complex, analyzed by sucrose gradient velocity sedimentation following octyl-beta-D-glucopyranoside extraction. Caveolin-1 alpha interacts with caveolin-1beta, caveolin-2, actin, the microsomal form of NADH cytochrome B5 reductase and ESA/reggie-1/flotillin-2 as shown by co-immunoprecipitation. We propose the concept that ATP biosynthesis in caveolae regulates mechanosignaling and is induced by membrane depolarization and a proton gradient. Pressure stimuli and metabolic changes may trigger gene regulation in endothelial cells, involving a nuclear conformer of caveolin-1, shown here with an epitope-specific caveolin-1 antibody, and immediate response of ion channel activity, regulated by ESA/reggie-1/flotillin-2.
 ...
PMID:Caveolae: biochemical analysis. 1529 82

Time-dependent changes in the cell death mode from apoptosis to necrosis were studied in cultured 143B cells treated with menadione, an anti-cancerous drug, excluding a possible involvement of "secondary necrosis." The population of apoptotic cells judged by FITC-Annexin V and propidium iodide (PI) double staining reached its maximum at 6 hours after 100 microM menadione treatment followed by an abrupt decrease thereafter, while that of necrotic cells continuously increased reaching 90% at 24 hours. Electron microscopically, cells attached to the culture dish at 6 hours after the treatment consisted of two different types of cells: cells with typical apoptotic features occupying the major population and those with condensed nuclei and swollen cytoplasm. Cells attached to the culture dish at 8 hours after the treatment consisted exclusively of those with condensed nuclei and swollen cytoplasm. Mitochondria in these cells showed various structural changes: those swollen to various degrees with deposition of flocculent densities, or those with highly condensed matrix. Distinct decreases both in intracellular levels of ATP and caspase-3-like activities and remarkable elevations of intracellular levels of superoxide, which were partly suppressed by NAD(P)H oxidase inhibitors, occurred at 6 hours after the treatment. These results may suggest that distinct increases of the intracellular level of superoxide derived from plasma membrane NAD(P)H oxidase besides that from mitochondria have triggered the transition of cell death mode from apoptosis to necrosis. Transition of highly condensed mitochondria to extremely swollen ones may reflect necrotic processes in menadione-treated cells. The present study strongly suggests that time-dependent study is essential using the electron microscopic technique to analyze detailed processes in the changes of the cell death mode.
 ...
PMID:The switch mechanism of the cell death mode from apoptosis to necrosis in menadione-treated human osteosarcoma cell line 143B cells. 1545 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>