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

Annexins comprise a family of proteins that exhibit a Ca2+-dependent binding to phospholipid membranes that is possibly relevant to their in vivo function. Although substantial structural information about the ternary (protein/lipid/Ca2+) interaction in bulk phases has been derived from a variety of techniques, little is known about the temporal and spatial organization of ternary monolayer films. The effect of Ca2+ on the interactions between annexin V (AxV) and anionic DMPA monolayers was therefore investigated using three complementary approaches: surface pressure measurements, infrared reflection-absorption spectroscopy (IRRAS), and Brewster angle microscopy (BAM). In the absence of Ca2+, the injection of AxV into an aqueous subphase beneath a DMPA monolayer initially in a liquid expanded phase produced BAM images revealing domains of protein presumably surrounded by liquid-expanded lipid. The protein-rich areas expanded with time, resulting in reduction of the area available to the DMPA and, eventually, in the formation of condensed lipid domains in spatial regions separate from the protein film. There was thus no evidence for a specific binary AxV/lipid interaction. In contrast, injection of AxV/Ca2+ at a total Ca2+ concentration of 10 microM beneath a DMPA monolayer revealed no pure protein domains, but rather the slow formation of pinhead structures. This was followed by slow (>2 h) rigidification of the whole film accompanied by an increase in surface pressure, and connection of solid domains to form a structure resembling strings of pearls. These changes were characteristic of this specific ternary interaction. Acyl chain conformational order of the DMPA, as measured by nu(sym)CH2 near 2850 cm(-1), was increased in both the AxV/DMPA and AxV/DMPA/Ca2+ monolayers compared to either DMPA monolayers alone or in the presence of Ca2+. The utility of the combined structural and temporal information derived from these three complementary techniques for the study of monolayers in situ at the air/water interface is evident from this work.
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PMID:Domain structure and molecular conformation in annexin V/1,2-dimyristoyl-sn-glycero-3-phosphate/Ca2+ aqueous monolayers: a Brewster angle microscopy/infrared reflection-absorption spectroscopy study. 963 81

Annexin V (AxV) is a member of a family of proteins that exhibit functionally relevant Ca2+-dependent binding to anionic phospholipid membranes. Protein structure and stability as a function of Ca2+ and phospholipids was studied by bulk phase infrared (IR) spectroscopy and by IR reflection-absorption spectroscopy (IRRAS) of monolayers in situ at the air/water (A/W) interface. Bulk phase experiments revealed that AxV undergoes an irreversible thermal denaturation at approximately 45-50 degreesC, as shown by the appearance of amide I bands at 1617 and 1682 cm-1. However, some native secondary structure is retained, even at 60 degreesC, consistent with a partially unfolded "molten globule" state. Formation of the Ca2+/phospholipid/protein ternary complex significantly protects the protein from thermal denaturation as compared to AxV alone, Ca2+/AxV, or lipid/AxV mixtures. Stabilization of AxV secondary structure by a DMPA monolayer in the presence of Ca2+ was also observed by IRRAS. Spectra of an adsorbed AxV film in the presence or absence of Ca2+ showed a 10 cm-1 shift in the amide I mode, corresponding to loss of ordered structure at the A/W interface. In both the bulk phase and IRRAS experiments, protection against H-->D exchange in AxV was enhanced only in the ternary complex. The combined data suggest that the secondary structure of AxV is strongly affected by the Ca2+/membrane component of the ternary complex whereas lipid conformational order is unchanged by protein.
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PMID:Stability of annexin V in ternary complexes with Ca2+ and anionic phospholipids: IR studies of monolayer and bulk phases. 988 20

Annexins, protein kinases C and cytosolic phospholipase A2 belong to three families of ubiquitous cytoplasmic proteins involved in signal transduction. All annexins share the property of binding to phospholipids in the presence of calcium. Most annexins are substrates for protein kinases C except annexin V, the most ubiquitous and abundant annexin. Protein kinases C (PKC) belong to three distinct groups of kinases, conventional PKCs (cPKCs) that depend on calcium, diacylglycerol and negatively charged phospholipids for their activity, novel PKCs (nPKCs) and atypical PKCs (aPKCs), that do not require calcium for their activity, although they both require negatively charged phospholipids. Cytosolic phospholipase A2 (cPLA2) depends on calcium for its catalytic activity as well as on serine phosphorylation by MAP kinases. We report that annexin V modulates the activity of cPKCs as well as of cPLA2 by interfering with their ability to bind to negatively charged phospholipids and calcium. We propose that annexin V could interfere with the calcium and phospholipid signalling pathway.
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PMID:Annexin V and phospholipid metabolism. 1035 74

Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro. But the biologic mechanism of this inhibition remains to be determined. We explored the possibility that an antiproliferative activity of progesterone in breast cancer cell lines is due to its ability to induce apoptosis. Since p53, bcl-2 and survivin genetically control the apoptotic process, we investigated whether or not these genes could be involved in the progesterone-induced apoptosis. We found a maximal 90% inhibition of cell proliferation with T47-D breast cancer cells after exposure to 10 microM progesterone for 72 h. Control progesterone receptor negative MDA-231 cancer cells were unresponsive to 10 microM progesterone. The earliest sign of apoptosis is translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane and can be monitored by the calcium-dependent binding of annexin V in conjunction with flow cytometry. After 24 h of exposure to 10 microM progesterone, cytofluorometric analysis of T47-D breast cancer cells indicated 43% were annexin V-positive and had undergone apoptosis and no cells showed signs of cellular necrosis (propidium iodide negative). After 72 h of exposure to 10 microM progesterone, 48% of the cells had undergone apoptosis and 40% were annexin V positive/propidium iodide positive indicating signs of necrosis. Control untreated cancer cells did not undergo apoptosis. Evidence proving apoptosis was also demonstrated by fragmentation of nuclear DNA into multiples of oligonucleosomal fragments. After 24 h of exposure of T47-D cells to either 1 or 10 microM progesterone, we observed a marked down-regulation of protooncogene bcl-2 protein and mRNA levels. mRNA levels of survivin and the metastatic variant CD44 v7-v10 were also downregulated. Progesterone increased p53 mRNA levels. These results demonstrate that progesterone at relative high physiological concentrations, but comparable to those seen in plasma during the third trimester of human pregnancy, exhibited a strong antiproliferative effect on breast cancer cells and induced apoptosis.
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PMID:Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis. 1070 95

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells may be impacted by immunosuppressive agents. We examined this for mycophenolate mofetil (MMF) compared with cyclosporine (CYA). Peripheral blood leukocytes (PBL) were stimulated by either Staph enterotoxin B (SEB) or by anti-CD3 plus anti-CD28. Cell division analysis (sequential reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations. Apoptosis was measured by annexin V staining, and FasL expression by anti-FasL antibody staining, of activated cells using flow cytometry. CSA and mycophenolic acid (MPA, the active agent of MMF) were added in titration in 3-day cultures. We found that CSA caused diminution in apoptosis but MPA increased it with SEB stimulation. The CSA effect on apoptosis was present when a more calcineurin-dependent stimulus. anti-CD3+ anti-CD28, was used but the MPA effect was less, producing a decrease only in the undivided cells. To look more directly at the differential effect on calcineurin-dependent AICD gene induction of the two agents, we measured Fas-L expression with anti-CD-3 + CD28 stimulation, and confirmed that CYA caused a major decrement in appearance of Fas-L, whereas MPA caused a converse accumulation of it. This seems to be explained by the block more distal in cell activation, resulting in a build-up of a precursor in the activation pathways. We conclude that MMF treatment may be rationale as an adjunct to calcineurin inhibitor treatment because of its converse effect on T cell regulatory apoptosis.
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PMID:Positive effect on T-cell regulatory apoptosis by mycophenolate mofetil. 1190 84

The clinically relevant polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) inhibits cell growth by down-regulating polyamine biosynthesis, up-regulating polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase (SSAT), and depleting intracellular polyamine pools. Among human melanoma cell lines, the analogue causes rapid apoptosis in SK-MEL-28 cells and a sharp G(1) arrest in MALME-3M cells. This study reveals that DENSPM potently activates the mitogen-activated protein kinase (MAPK) pathways in melanoma cells and investigates the role of this response in determining cellular outcomes. Onset of apoptosis was preceded by an intense phosphorylation of the MAPKs, including extracellular signal-regulated kinase 1/2, c-Jun NH(2)-terminal kinase, and p38 in both SK-MEL-28 and MALME-3M cells. A panel of DENSPM analogues differing only in their ability to induce SSAT was used to show that MAPK activation was causally linked to induction of SSAT activity and related oxidative events. The latter was confirmed with the polyamine oxidase inhibitor MDL-75275 and the antioxidant N-acetyl-L-cysteine, which when used in combination with DENSPM, decreased MAPK activation and as previously shown, reduced apoptosis. The MAP/extracellular signal-regulated kinase-1 inhibitor PD 98059 reduced activation of all three kinases but failed to alter apoptosis in DENSPM-treated SK-MEL-28 cells. By contrast, the inhibitor prevented p21(waf1/cip1) induction and enhanced apoptosis in MALME-3M cells as indicated by accelerated caspase-3 activation and positive annexin V staining. The generality of this effect was demonstrated in DENSPM-treated A375 and LOX human melanoma cells. Taken together, the importance of the MAPK pathways in determining the biological response to DENSPM treatment is dependent on the genetic environment of the cell.
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PMID:The role of mitogen-activated protein kinase activation in determining cellular outcomes in polyamine analogue-treated human melanoma cells. 1283 50

Annexin V is a Ca(2+)-dependent phospholipid-binding protein belonging to the annexin family whose regulation is currently not well understood. In this study, we utilized anisomycin, a protein synthesis inhibitor that activates MAP kinases (MAPKs), to examine the role of MAPKs in annexin V expression in the MCAS ovarian carcinoma cell line. A one-step real-time TaqMan-based reverse transcriptase-PCR method was developed to quantify annexin V mRNA expression. We found that annexin V was induced 13.3-fold by anisomycin and that this superinduction was attenuated by pretreatment with the MEK inhibitors, U0126 and PD98059, but not with the p38 MAPK inhibitor, SB203580. In addition, immunoblotting showed that anisomycin stimulated the phosphorylation of ERK1/2 as well as p38 MAPK and that the phosphorylations were blocked by the three kinase inhibitors. Taken together, these results suggest that anisomycin superinduces annexin V mRNA expression through the ERK1/2 MAPK pathway, but not through the p38 MAPK pathway.
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PMID:Anisomycin superinduces annexin V mRNA expression through the ERK1/2 but not the p38 MAP kinase pathway. 1470 38

PTPA, which possesses a peptidyl prolyl isomerase activity, was initially isolated as a protein that stimulates the weak phosphotyrosyl phosphatase activity of the Ser/Thr phosphatase PP2A. Here we show that transient overexpression of PTPA leads to cell death in a time-dependent manner in mammalian cells. PTPA-overproducing cells manifest hallmarks of apoptosis including chromatin condensation, membrane blebbing, positive staining with annexin V, dephosphorylation of Bad, and caspase-3 cleavage. Incubation of cells with the PP2A inhibitor okadaic acid does not prevent either dephosphorylation of Bad or PTPA-induced apoptosis, indicating that PTPA is unlikely to mediate its proapoptotic effect via PP2A. Moreover, we find no evidence for the involvement of either p53 or MAP kinases. Our data reveal a potential novel role for PTPA in the apoptotic process.
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PMID:Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. 1733 20

Methyl angolensate (MA), a natural tetranortriterpenoid, purified from Soymida febrifuga is examined for the first time for its anticancer properties. We find that MA inhibits growth of T-cell leukemia and chronic myelogenous leukemia cells in a time- and dose-dependent manner. Accumulation of cells in the subG1 peak, annexin V binding and DNA fragmentation suggested induction of apoptosis. Besides, upregulation of BAD (proapoptotic) and downregulation of BCL2 (antiapoptotic) gene products further supported induction of apoptosis. Loss of mitochondrial membrane potential, activation of caspase 9, caspase 3, cleavage of PARP, downregulation of Ku70/80 and phosphorylation of MAP kinases suggested that MA could induce intrinsic pathway of apoptosis in leukemic cells.
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PMID:Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells. 1902 52

Arsenic trioxide, As(2)O(3), has successfully been used to treat acute promyelocytic leukemia (APL). Induction of apoptosis in cancerous cells has been proposed to be the underlying mechanism for the therapeutic efficacy of arsenic. To further understand the cytotoxicity of arsenic compounds in APL cells, HL-60 cells were exposed to graded concentrations of the following arsenicals for up to 48 h: arsenic trioxide (As(III)), sodium arsenate (As(V)), phenylarsine oxide (PAO(III)), monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and the viability and modes of cell death assessed. The arsenic-exposed cells were stained with annexin V-PE and 7-aminoactinomycin D (7-AAD) and analyzed by flow cytometry in order to detect apoptotic and viable cells while cell morphology was visualized using scanning and transmission electron microscopy. Acridine orange staining and microtubule-associated protein 1 light chain 3 (MAP-LC3) detection were used to recognize autophagic cell death. The results showed that the compounds reduced viable HL-60 cells by inducing apoptosis in a concentration-dependent manner. None of the compounds tested caused a significant change in binding of acridine orange or redistribution of MAP-LC3. Potencies of the six different arsenic compounds tested were ranked as PAO(III)>MMA(III)> or =As(III)>As(V)>MMA(V)>DMA(V). An increase in caspase-3 activity by PAO(III), MMA(III) and DMA(V) implied that these compounds induced apoptosis in HL-60 cells through a caspase-dependent mechanism, but the other arsenic compounds failed to activate caspase-3, suggesting that they induce apoptosis by an alternative pathway.
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PMID:Differential cytotoxic effects of arsenic compounds in human acute promyelocytic leukemia cells. 1946 42


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