Disease relevance of Anxa5

• Mouse annexin V genomic organization includes an endogenous retrovirus [1].
• Effects of Phytolacca acinosa polysaccharides I (PAP-I), 5 approximately 40 mg/kg in timing of 7 times/wk, 3 times/wk and 1 time/wk on their antitumor efficiency in Sarcoma-180 bearing mice were comparatively investigated [2].
• Here, we report that AxV preferentially targets irradiated lymphoma cells to CD8+ dendritic cells for in vivo clearance, elicits the release of proinflammatory cytokines and dramatically enhances the protection elicited against the tumor [3].
• The in vivo antithrombotic activities of the most active constructs were 3- to 10-fold higher than that of ANV in a mouse arterial thrombosis model [4].
• Previously, we have found that human liver annexin V (hA-V; in earlier reports referred as Endonexin II) is a specific hepatitis B surface antigen (HBsAg) binding protein [5].

Psychiatry related information on Anxa5

• The numbers in thymocytes, especially CD4(+)CD8(+) population, were decreased significantly and apoptotic cells, as assessed by Annexin V expression, were reciprocally increased after the exposure to the psychological stress [6].

High impact information on Anxa5

• Annexin-V binds to externalized phosphatidylserine (PS) of cells undergoing programmed cell death [7].
• Caspase inhibitors decreased the number of annexin-V-positive cardiomyocytes and slowed down the rate of PS exposure of cardiomyocytes that still bound annexin-V [7].
• We show here that LCMV-specific T cells in peripheral tissue (peritoneal cavity, lung, fat pads) reacted much less with the apoptotic marker Annexin-V than those in spleen and lymph nodes [8].
• Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages [3].
• 5'-bromo-2'-deoxyuridine incorporation and annexin V staining establish a role for Brg1 complexes in the regulation of thymocyte cell proliferation and survival [9].

Chemical compound and disease context of Anxa5

• In vivo, annexin V had a significant protective effect against spleen weight loss in mice treated by an alkylating agent previously shown to induce lymphocyte apoptosis [10].
• Next, we analyzed the influence of AxV on chronic macrophage infection with HIV-1, known to expose PS on its surface [11].
• Transfection with constitutive active GSK3betaS9A sensitized neonatal cardiomyocytes to hypoxia/reoxygenation-induced apoptosis as measured by annexin V/propidium iodide staining [12].
• MATERIALS AND METHODS: Annexin V labeled with an indocyanine fluorophore (bisfunctional succinimidyl ester of cyanine 5.5) (Amersham, Little Chalfont, United Kingdom) was injected intravenously in mice 18 hours after the repair of unilateral 720-degree testicular torsion for 2 hours [13].
• Monitoring of splenocyte apoptosis by determination of Annexin V binding revealed an increase in splenocyte apoptosis 24 h after hemorrhage in the HEM group but not in the animals pretreated with propranolol or metoprolol [14].

Biological context of Anxa5

• Therefore, expression of the Anxa5 gene may represent a novel marker characterizing cell lineages involved in the development of the vascular as well as the skeletal system [15].
• When anxA5 binds to the PtdSer-expressing membranes during apoptosis, it crystallizes as an extended two-dimensional network and activates thereby a novel portal of cell entry that results in the internalization of the PtdSer-expressing membrane patches [16].
• This down-regulation depends on the abilities of anxA5 to bind to PtdSer and to form a two-dimensional crystal at the membrane [16].
• The intensively studied annexin A5 has been identified by its effects on blood coagulation, and subsequently, its function as a calcium-specific ion channel was described [17].
• Myotube formation in vitro can be inhibited by the PS binding protein annexin V, in contrast to its mutant M1234, which lacks the ability to bind to PS [18].

Anatomical context of Anxa5

• This mechanism may be part of a more general autocrine function of anxA5 to regulate the plasma membrane receptor repertoir under stress conditions associated with the surface expression of PtdSer [16].
• We extended our in vitro work to the in vivo situation and show in a mouse model that anxA5 causes the down-regulation of TF expression by smooth muscle cells of the media of the carotid artery that was mechanically injured [16].
• Neither the development of skeletal elements nor the in vitro calcification properties of isolated chondrocytes is significantly impaired by the absence of annexin A5 [17].
• 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 [19].
• The apoptotic pathway, which was followed through binding of cells to Annexin V, activation of caspase-3 and fragmentation of DNA, involved destabilization of mitochondria, probably as a result of downregulation of PKC and Bcl-2 [20].

Associations of Anxa5 with chemical compounds

• FACS analysis of cells isolated from the CNS showed significantly fewer annexin V/propidium iodide-positive lymphocytes in the CNS of P2X7R-/- mice early in the disease, and TUNEL staining of inflamed CNS tissues supported this result [21].
• We found by BrdU pulse-chase, cell cycle, and annexin V analyses that IL-7 administration has significant proliferative and antiapoptotic effects on posttransplant peripheral T cells [22].
• The effect of imatinib on cell growth and apoptosis was examined with an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay and with a morphologic test and Annexin V staining, respectively [23].
• Angiostatin-induced apoptosis was confirmed by endothelial cell nuclear acridine orange incorporation as well as by annexin V and TUNEL staining [24].
• Okadaic acid inhibits protein phosphatase 4 (PP4), a novel PP2A-related serine/threonine phosphatase, at a 50% inhibitory concentration (IC(50)) comparable to that for PP2A [25].

Physical interactions of Anxa5

• Moreover, flow cytometry analysis of hypodiploid DNA and annexin V binding revealed that ligation of Ly49A protected cells from apoptosis induced by anti-CD3 mAbs or Ag [26].
• The influence of lactosyl residues contained in branched O-glycans or complex N-glycans on galectin 1 binding and induction of annexin V ligand in murine CD8 T cells was assessed [27].
• An Annexin-V binding assay was used to evaluate the susceptibility of corneal cells to both Fas-dependent and CD4 T-cell-mediated apoptosis in vitro [28].
• Similarly, apoptosis induction measured by Annexin V binding and Caspase 3 activity was detected later after incubation of cells with PK1 or alpha-CD71 targeted conjugate [29].
• SLP-76(-/-) platelets also exhibited less annexin V binding than SLP-76(+/-) platelets after costimulation with thrombin and convulxin (P <.05) [30].

Regulatory relationships of Anxa5

• In conclusion, anxA5 down-regulates surface-expressed TF by activating the novel portal of cell entry [16].
• PAP-I enhanced the production of IL-2 and NKCF [31].
• The effect of CA-MEK on sodium butyrate (NaB)-induced apoptosis was evaluated by the Annexin V assay [32].
• Furthermore, the addition of agonistic Fas antibody-(Jo2)-induced cholangiocyte apoptosis confirmed by DNA-ladder formation and annexin V staining [33].
• The Met inhibitor induced G(1) cell cycle arrest and apoptosis with increased Annexin V staining and caspase 3 activity [34].

Other interactions of Anxa5

• We furthermore show that THP-1 cells produce and externalize anxA5 that cause the internalization of TF in an autocrine type of mechanism [16].
• Fas expression and apoptosis were determined by FACScan analysis of phycoerythrin-anti-Fas mAb staining and annexin V staining, respectively [35].
• LPS-induced cytotoxicity, poly(ADP-ribose) polymerase cleavage, and annexin V staining were also highest in p60-/- p80-/- cells and lowest in wt cells [36].
• Further studies on IL-1, TNF and IL-6 secreted from macrophages and the level of CSF activity in serum of normal mice with different schedules showed that PAP-I (10 mg/kg, 3 time/wk) was the best one in regulating the production of IL-1, TNF, IL-6 and CSF activity [2].
• A variety of assays were used to assess the progression of apoptosis: DNA size analysis on agarose gel electrophoresis, flow cytometry with annexin V/PI staining, and analysis of expression levels of Bcl-2 family and NF-kappaB mRNA and proteins by RT-PCR, Western blotting, and EMSA [37].

Analytical, diagnostic and therapeutic context of Anxa5

• Mouse annexin V genomic clones were characterized by restriction analysis, Southern blotting and DNA sequencing [1].
• Immunohistochemistry, in situ hybridization and reporter gene expression were used to define expression of annexin A5 during early mouse development [15].
• METHODS: Apoptosis in murine TECs was determined by FACS with annexin-V or ligation-mediated-polymerase chain reaction (LM-PCR) and mRNA levels by reverse transcription (RT)-PCR or Northern blot [38].
• The Cd induced DNA damage as depicted by internucleosomal fragmentation on agarose and histone associated mono- and oligonucleosomes detection by ELISA, corrobated with the apoptotic DNA (sub-G(1) population) and total apoptotic cells by Annexin V binding assay [39].
• Splenocytes from mice injected ip with PAP-I, 5, 10 and 50 mg.kg-1, thrice a week produced more cytotoxicity against P815 and L929 tumor cells compared with the control group [40].

References