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)

Annexins of human placenta have been purified and characterized. In addition to annexins I to VI and II complex, two novel species of 45 and 68 kDa were obtained. Annexins V and II are most abundant. Phospholipase A2 inhibitory activity of annexin V is low in contrast to that of annexins I to VI, and it is best for annexin II complex. In vitro, annexins bind to liposomes to extents which depend on the type of phospholipid used. This induces liposome aggregation whereby Mix, PI, and PC liposomes preferably aggregate. This hinders PLA2 from its access to the substate. Our data suggest that substrate-depletion by annexins is rather the result of liposome cross-bridging than pure liposome surface coating.
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PMID:Annexins and phospholipase A2 inhibition. 144 24

We established a method for measuring procoagulant action on human umbilical vein endothelial cells (HUVEC). HUVEC (2.5 x 10(4)/well) were stimulated with 1 microgram/ml endotoxin (lipopolysaccharide: LPS) for 6 hours at 37 degrees C in 5% CO2. After washing, the HUVEC were incubated with assay buffer containing Proplex ST 1 unit (factor VII)/ml, S2222 0.6 mg/ml and CaCl2 6.6 mM, for 30 minutes at 37 degrees C. The procoagulant activity was determined by measuring the supernatant at OD405. Calphobindin I, II and III (CPB I, CPB II and CPB III) are the calcium dependent phospholipid binding proteins that exhibit anticoagulant activity in vitro. In this study, we investigated the effects of CPB I, CPB II and CPB III on procoagulant activity (PCA) expressed on HUVEC. The results are as follows 1) CPBI inhibits the procoagulant activity on HUVEC in a dose-dependent manner (IC 50% less than 0.4 microM). The same doses (0.4 microM) of CPBII and CPBIII decreased the procoagulant activity to 28.1% (CPBII), and to 84.6% (CPB III). CPB anticoagulant activities were, CPBII greater than CPBI greater than CPBIII, in that order. 2) When 0.05% H2O2 was added to the cell culture medium wells, concentrations of CPBI in supernatants increased in a time-dependent manner, and they reached to the maximum after 8 hours. CPBI in supernatants after 24 hours were not detected without H2O2, but concentrations of 4.88 ng/ml/10(4) cells with 0.01% H2O2, and 9.60 ng/ml/10(4) cells with 0.05% H2O2 were detected.
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PMID:[Effect of coagulation inhibitor proteins (Calphobindins) on tissue factor expression of endothelial cells]. 145 41

The quaternary structure of annexin V, a calcium-dependent phospholipid binding protein, was investigated by chemical cross-linking. Calcium was found to induce the formation of trimers, hexamers, and higher aggregates only when anionic phospholipids were present. Oligomerization occurred under the same conditions annexin-vesicle binding. A model is proposed in which cell stimulation leads to calcium-induced organization of arrays of annexin V lining the inner membrane surface, thus altering properties such as permeability and fluidity.
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PMID:Annexin V forms calcium-dependent trimeric units on phospholipid vesicles. 145 45

The subcellular localization of annexin V in cultured human umbilical vein endothelial cells, epithelial cells and fibroblasts was examined. Indirect immunofluorescence and immunoblotting studies using affinity-purified anti-annexin V antibodies revealed that annexin V is located within the cytoplasm and nucleus of these cells. Further examination and direct binding studies showed that annexin V within the nucleus is associated with the nucleolus. These findings suggest that annexin V may play a role in a nucleolar function, such as ribosome assembly and transport.
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PMID:Nucleolar and cytoplasmic localization of annexin V. 146 79

Arachidonic acid is mobilized from fetal membrane phospholipids at parturition leading to increased production of oxytocic prostaglandins which may initiate or maintain myometrial contractions. Phospholipid mobilization requires activation of phospholipase A2 or C, both of which require calcium for activity. The annexins (lipocortins) are a superfamily of proteins which bind to calcium and phospholipids and thereby may alter phospholipase activity through two mechanisms: modulation of intracellular free Ca2+ concentrations or regulation of the accessibility of phospholipids to hydrolyzing enzymes. Using Western immunoblotting with monospecific polyclonal antibodies, annexins I-VI were identified in human amnion and chorion/decidua at term in tissues obtained from patients in labor or not in labor. Each annexin was present in two distinct pools: a pool which only associated with the membrane in the presence of calcium (calcium-dependent pool) and a calcium-independent pool that remained membrane bound in the presence of calcium chelators. Annexin I was present as two species, resolving at 36 kDa and 68 kDa. The total concentration of annexin I in both amnion and chorion/decidua was significantly decreased with labor, while the total concentration of annexin V in chorion significantly increased with labor. The size of individual pools of annexins also changed with labor: the calcium-dependent pool of annexins I and II in both amnion and chorion significantly decreased; the calcium-dependent pool of annexin V increased in chorion; and calcium-independent pools of annexin I in amnion and annexins I, II, and V in chorion significantly decreased with labor. The decrease in total annexin I concentration with labor in amnion reflects a substantial decrease (80-90%) in the pool tightly bound to the membrane in a calcium-independent manner. This striking change distinguishes annexin I as a potential candidate inhibitor which is specifically downregulated at parturition, potentially leading to increased access of phospholipases to substrate phospholipids and increased prostaglandin production at labor.
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PMID:Changes in annexin (lipocortin) content in human amnion and chorion at parturition. 146 69

Stimulation of cardiac phospholipid metabolism has diverse biological effects, ranging from subtle changes in cellular function to severe cellular damage. Accordingly, knowledge of the factors governing the activity of cardiac phospholipases is of great biological importance. A possible role of annexins, intracellular proteins that bind to membranes in a calcium dependent manner, as modulators of phospholipase activity has been proposed. In this study we investigated the cell type specific distribution of Annexin V and VIII in the heart. Recombinant Annexin V was used to examine the effect of this type of Annexin on cardiac phospholipase activity. Western blot analysis shows that annexin V is abundantly present in the heart. Using isolated myocytes and cultured cardiac endothelial and fibroblast-like cells, it is demonstrated that the localization of Annexin V is confined to non-myocytes. No positive bands matching the Mw of recombinant Annexin VIII are found in any of the cell types examined. In vitro studies demonstrate that recombinant Annexin V potently inhibits the activity of cardiac membrane-bound phospholipases, acting on their natural surrounding substrate, in a calcium dependent manner. Interestingly, annexin V also inhibits triacylglycerol hydrolysis. In conclusion, the expression of annexins is cell-type specific and suggests a cell-type specific function of these proteins in the heart. The absence of Annexin V in cardiac myocytes dismisses involvement of this annexin in cardiomyocyte phospholipid metabolism. The presence of Annexin V in cardiac endothelial and fibroblasts suggests a regulating role in the phospholipid homeostasis of non-myocyte cell types in the heart.
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PMID:Annexins in cardiac tissue: cellular localization and effect on phospholipase activity. 148 Jan 59

The distribution of annexin V isoforms (CaBP33 and CaBP37) and of annexin VI in bovine lung, heart, and brain subfractions was investigated with special reference to the fractions of these proteins which are membrane-bound. In addition to EGTA-extractable pools of the above proteins, membranes from lung, heart, and brain contain EGTA-resistant annexins V and VI which can be solubilized with detergents (Triton X-100 or Triton X-114). A strong base like Na2CO3, which is usually effective in extracting membrane proteins, only partially solubilizes the membrane-bound, EGTA-resistant annexins analyzed here. Also, only 50-60% of the Triton X-114-soluble annexins partition in the aqueous phase, the remaining fractions being recovered in the detergent-rich phase. Altogether, these findings suggest that, by an as yet unknown mechanism, following Ca(2+)-dependent association of annexin V isoforms and annexin VI with membranes, substantial fractions of these proteins remain bound to membranes in a Ca(2+)-independent way and behave like integral membrane proteins. These results further support the possibility that the above annexins might play a role in membrane trafficking and/or in the regulation of the structural organization of membranes.
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PMID:Membrane-bound annexin V isoforms (CaBP33 and CaBP37) and annexin VI in bovine tissues behave like integral membrane proteins. 153 Nov 31

Annexins represent a widespread family of Ca(++)-dependent phospholipid binding proteins. Although their precise functions are still unknown, they probably play an important role in cell regulation because they are major substrates for various growth factor receptor kinases. We characterized annexins in human skin using three different antisera raised against annexin II, annexin V, and a synthetic peptide that resembles the consensus sequence of all annexins. In normal human skin, using SDS-PAGE, two-dimensional gel electrophoresis and immunoblot analysis, we identified two major 34-kDa proteins and one 36-kDa protein, with respective isoelectric points of 6.5, 5.2, and 7.2-7.9. According to these criteria they were identified as annexins, I, V, and II, respectively. Minor 45-51 kDa and 68-kDa proteins with 6.1-6.7 and 6.8-7.1 isoelectric points were also present, and likely corresponded to annexins VII and VI, respectively. We investigated the ability of these proteins to bind phospholipids in the presence of calcium using liposomes formed from a mixture of phosphatidylserine and phosphatidylcholine. The cellular distribution of annexins in normal human skin was determined by immunofluorescence with antiannexin II and anti-annexin V antibodies. Labeling with both antibodies was observed predominantly at the cell membrane with some cytoplasmic staining also being apparent. Specificity was confirmed by the absence of staining using pre-immune sera or after the absorption of the antibodies with their corresponding antigens. These proteins were also characterized in vitro in a reconstituted human skin model. All were present in this system except annexin VI and VII, which were lost after phospholipid purification. Further experiments should now be carried out using this system to clarify the role and regulation of these proteins within the epidermis.
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PMID:Characterization and subcellular localization of calcium-dependent phospholipid binding proteins (annexins) in normal human skin and reconstituted epidermis. 153 82

Antiphospholipid antibodies provide a model for immune-mediated thrombosis. Study of the pathophysiological effects of antiphospholipid antibodies has revealed several potential thrombotic mechanisms. Experiments designed to elucidate these mechanisms have used both in vitro and in vivo techniques. Results implicate endothelial anticoagulant dysfunction, abnormalities of prostacyclin, antithrombin III, placental anticoagulant protein, proteins C and S, and complement activation, any of which could lead to thrombosis. In an individual patient, thrombosis may result from a combination of these abnormalities or it may require the presence of other nonimmune-mediated perturbations of the coagulation system.
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PMID:Antiphospholipid antibodies: origin, specificity, and mechanism of action. 156 68

The annexins are a widespread family of calcium-dependent membrane-binding proteins. No common function has been identified for the family and, until recently, no crystallographic data existed for an annexin. In this paper we draw together 22 available annexin sequences consisting of 88 similar repeat units, and apply the techniques of multiple sequence alignment, pattern matching, secondary structure prediction and conservation analysis to the characterisation of the molecules. The analysis clearly shows that the repeats cluster into four distinct families and that greatest variation occurs within the repeat 3 units. Multiple alignment of the 88 repeats shows amino acids with conserved physicochemical properties at 22 positions, with only Gly at position 23 being absolutely conserved in all repeats. Secondary structure prediction techniques identify five conserved helices in each repeat unit and patterns of conserved hydrophobic amino acids are consistent with one face of a helix packing against the protein core in predicted helices a, c, d, e. Helix b is generally hydrophobic in all repeats, but contains a striking pattern of repeat-specific residue conservation at position 31, with Arg in repeats 4 and Glu in repeats 2, but unconserved amino acids in repeats 1 and 3. This suggests repeats 2 and 4 may interact via a buried saltbridge. The loop between predicted helices a and b of repeat 3 shows features distinct from the equivalent loop in repeats 1, 2 and 4, suggesting an important structural and/or functional role for this region. No compelling evidence emerges from this study for uteroglobin and the annexins sharing similar tertiary structures, or for uteroglobin representing a derivative of a primordial one-repeat structure that underwent duplication to give the present day annexins. The analyses performed in this paper are re-evaluated in the Appendix, in the light of the recently published X-ray structure for human annexin V. The structure confirms most of the predictions and shows the power of techniques for the determination of tertiary structural information from the amino acid sequences of an aligned protein family.
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PMID:Amino acid sequence analysis of the annexin super-gene family of proteins. 164 19


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