Disease relevance of ANXA5

• ANXA1 and ANXA5 were also expressed in abundance in the astrocytoma [1].
• As a prelude to examining the potential role of ANXA1 in the pathophysiology of pituitary tumours, this study examined the expression, phosphorylation status and distribution of ANXA1 and the closely related protein, annexin 5 (ANXA5), in a series of pituitary adenomas and in two carcinomas [1].
• In comparison with the adenomas, the GH-secreting carcinoma showed abundant expression of both ANXA1 and ANXA5, with intense ANXA1 staining in some but not all tumour/endocrine cells [1].
• We cloned human endonexin II cDNA and expressed it in Escherichia coli [2].
• Human colon adenocarcinoma cell differentiation is associated with an up-regulation of AnxA1, AnxA2, and AnxA5 and with a subcellular relocation of these proteins [3].
• These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5 [4].

Psychiatry related information on ANXA5

• Time studies revealed that these cells went into apoptosis after prolonged incubation times up to 18 hours.Application of biotinilated annexin V for EM detection with gold-conjugated anti-biotin, showed that only clear-cut apoptotic, apoptotic necrotic and oncotic cells showed the gold-label at their membranes [5].
• Annexin V concentrations of the CSF did not correlate with dementia, duration of symptoms, age, sex, or treatment of PD [6].
• The radiolabelling efficiency of (124)I Annexin-V was 40% after 1 min reaction time [7].
• To understand the mechanism of annexin V-membrane interactions, we measured the interaction of human recombinant annexin V with phospholipid monolayers with differing head group and acyl group structures [8].

High impact information on ANXA5

• To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells [9].
• CONCLUSIONS: Antiphospholipid antibodies reduce the levels of annexin V and accelerate the coagulation of plasma on cultured trophoblasts and endothelial cells [9].
• The reduction of annexin V levels on vascular cells may be an important mechanism of thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome [9].
• Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome [9].
• Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies [9].

Chemical compound and disease context of ANXA5

• Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells [10].
• Residue-specific bioincorporation of 1,3-thiazolidine-4-carboxylic acid [thiaproline, Pro(S)], a non-natural amino acid analog of proline, into human recombinant annexin V was achieved with a proline-auxotrophic Escherichia coli strain by fermentation procedures in minimal medium [11].
• These neutrophils expose an alternative substrate for annexin-V different from PS and not recognized by macrophages, excluding early clearance as an explanation for the neutropenia [12].
• We have investigated the effects of enzastaurin on the viability of the cutaneous T-cell lymphoma cell lines HuT-78 and HH by using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, cell cycle analysis, propidium iodide and annexin-V staining, and caspase-3-mediated proteolytic activation [13].
• By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrated that NVB and vincristine (VCR) induced both mitotic arrest and apoptosis in leukemia and lymphoma cells, in a drug exposure time dependent manner [14].

Biological context of ANXA5

• The latter effect was confirmed using three distinct technical procedures, namely, cell cycle, Hoechst staining, and ANXA5 binding assay [15].
• The phosphatidylserine-annexin A5-mediated pinocytic pathway is not restricted to cells in apoptosis [16].
• The two-dimensional protein network of annexin A5 at the surface prevents apoptotic body formation without interfering with the progression of apoptosis as demonstrated by activation of caspase-3, PtdSer exposure, and DNA fragmentation [16].
• Transient transfection of nonsecreted YFP-wild-type IGFBP-3 decreased cell viability, as assessed by staining with annexin V followed by flow cytometry [17].
• Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein [2].

Anatomical context of ANXA5

• The annexin A5 protein network bends the membrane patch nanomechanically into the cell and elicits budding, endocytic vesicle formation, and cytoskeleton-dependent trafficking of the endocytic vesicle [16].
• AnxA1 and AnxA5 are mainly found in the cytoplasm while AnxA2 is localized underneath the plasma membrane in cell-to-cell contacts [3].
• Treatment of macrophages with VEGF-D induced apoptosis as determined by annexin V staining, by immunoblotting of activated caspase 3, and by the ratio of Bcl-2/Bax as well as by DNA fragmentation [18].
• 1. The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 microg ml(-1) phytohemagglutinin plus 2 U ml(-1) interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 microg ml(-1); 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining) [19].
• Using a bifunctional crosslinking reagent we have identified an 85-kDa complex in both membrane and cytoskeleton fractions containing annexin V and actin [20].

Associations of ANXA5 with chemical compounds

• Protein kinase C (PKC) blockade (PKC(19-36)) abolished the inhibitory effects of dexamethasone on forskolin-evoked peptide release and attenuated the antisecretory actions of ANXA1(Ac2-26.) ANXA5, which sequesters PKC in other systems, produced similar effects [21].
• Endonexin II is a protein with similar Ca2+ and phospholipid binding properties as lipocortin 1, but it is not a substrate for tyrosine kinases [22].
• Cell surface-expressed phosphatidylserine and annexin A5 open a novel portal of cell entry [16].
• Endonexin II was not phosphorylated by Ca2+/phospholipid-dependent enzyme (protein kinase C) even though it contained a threonine at a position analogous to the protein kinase C phosphorylation sites of lipocortin I, calpactin I, and protein II [2].
• Annexin V bound to heparin and heparan sulfate columns but not to chondroitin sulfate columns [23].

Physical interactions of ANXA5

• Binding of CRP to oxidized LDL did not interfere with binding of annexin A5, and vice versa [24].
• Immunoprecipitation using antibodies against annexin V copurify annexin V and gamma- but not beta-actin from activated platelets [20].
• The aim of the present study was to observe the effect of antibodies against ANXA5 (aANXA5) and antibodies against beta(2)GPI (abeta(2)GPI) on the binding of ANXA5 to the negatively charged phospholipid membrane [25].
• The data presented demonstrate that high-density cultured CR2-positive cells undergo apoptosis and that the redistribution and unmasking of Annexin V binding sites occurs in a fashion similar to the redistribution and unmasking of CR2 [26].
• In these cultured cells, engagement of CD33 resulted in an increased surface binding of annexin-V, followed by cell death [27].

Regulatory relationships of ANXA5

• Antiserum raised against VAC-beta weakly cross-reacts with VAC-alpha [28].
• Alpha v beta 5 integrin-dependent programmed cell death triggered by a peptide mimic of annexin V [29].
• 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 [30].
• HUVEC treated with zoledronate and TNF died without evidence of enhanced annexin-V binding, chromatin condensation, or nuclear fragmentation and caspase dependence [31].
• Annexin V inhibits the 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/extracellular signal-regulated kinase (ERK) signaling pathway upstream of Shc in MCF-7 cells [32].

Other interactions of ANXA5

• Annexin V is present in both cardiomyocytes and non-myocyte cell types in the heart and may play a role in the regulation of cellular ion fluxes, organization and secretion, while the cardiac effects of annexin II are unclear [33].
• CONCLUSIONS: The results demonstrate expression of both ANXA1 and ANXA5 in human pituitary tumours and thus raise the possibility that these proteins influence the growth and/or functional activity of the tumours [1].
• Annexin III or annexin V did not bind this receptor [34].
• The 73-kDa protein is related to the 67-kDa calelectrin and to lipocortin VI; the 32-kDa protein is different from endonexin I but related to chromobindin 7 and to lipocortin V [35].
• Only annexin IV and annexin V have unstructured cytoplasmic staining patterns consistent with predominantly cytosolic locations [36].

Analytical, diagnostic and therapeutic context of ANXA5

• Sequence analysis of 70 German RPL patients, all known to carry neither factor V Leiden nor a prothrombin mutation, revealed four consecutive nucleotide substitutions in the ANXA5 promoter, which were transmitted as a joint haplotype (M2) [37].
• Human annexin V (PP4), a member of the family of calcium, membrane binding proteins, has been crystallized in the presence of calcium and analysed by crystallography by multiple isomorphic replacement at 3 A and preliminarily refined at 2.5 A resolution [38].
• On the basis of the array results, we characterized apoptosis of normal and ET MKs by time-course evaluation of annexin-V and sub-G1 peak DNA stainings of immature and mature MKs after culture in serum-free medium with an optimal thrombopoietin concentration, and annexin-V-positive MKs only, with decreasing thrombopoietin concentrations [39].
• Characteristic features of apoptosis-like incorporation of propidium iodide (PI), such as increased annexin V binding, changes in mitochondrial membrane potential, and induction of DNA breaks (as evidenced by TUNEL techniques), could be induced in lymphoblasts after chlorpromazine treatment [40].
• Chemotactic activity (modified Boyden chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay), respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF functional activity [41].

References