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)

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.
 ...
PMID:Stability of annexin V in ternary complexes with Ca2+ and anionic phospholipids: IR studies of monolayer and bulk phases. 988 20

The conformational dynamics of domain III in annexin V bound to negatively charged phospholipid vesicles of 1-palmitoyl-2-oleoyl-sn-glycerophosphocholine and 1-palmitoyl-2-oleoyl-sn-glycerophosphoserine or incorporated into reverse micelles of water/sodium bis(2-ethylhexyl) sulfosuccinate in isooctane, used to mimic the phospholipid/water interface, was studied by steady-state and time-resolved fluorescence of its single tryptophan residue (W187). Upon interaction with sonicated phospholipid vesicles in the presence of calcium, or upon incorporation into reverse micelles without calcium, a progressive 12-14 nm red shift of the fluorescence emission spectrum of W187 is observed. The indole environment becomes therefore more polar than in the unbound protein. Three major lifetime populations describe the fluorescence intensity decays of W187 in both systems. A long-lived excited-state population characterizes the membrane-bound state of the protein. The existence of local conformers with different subnanosecond mobility is suggested by specific association between lifetimes and correlation times both for the protein in buffer and in interaction with the membrane surface. The interaction of the protein with the membrane surface preserves the existence of a rapid unhindered rotational motion, which is coupled with all three lifetimes. The longest lifetime is coupled to restricted motions in subnanosecond and nanosecond time scales. The overall amplitude of rotation of the indole ring is increased in the membrane-bound conformation of the protein. In reverse micelles, the local dynamics reported by W187 is also considerably increased whereas the overall folding of the protein remains unaffected. The same conformational change of domain III can therefore be provoked by different conditions: calcium binding at high concentration, mild acidic pH [Sopkova, J., Vincent, M., Takahashi, M., Lewit-Bentley, A. , and Gallay, J. (1998) Biochemistry 37, 11962-11970] and the interaction of the protein with the membrane surface. The high flexibility of domain III in the membrane-bound protein suggests that this domain may not be crucial for the interaction of the protein with the membrane, in contrast with previous models. Our data are compatible with atomic force microscopy results which suggest that domain III of annexin V does not interact strongly with the membrane surface [Reviakine, I., Bergma-Schutter, W., and Brisson, A. (1998) J. Struct. Biol. 121, 356-361].
 ...
PMID:Conformational flexibility of domain III of annexin V at membrane/water interfaces. 1022 Mar 32

Protein structure determination by classical x-ray crystallography requires three-dimensional crystals that are difficult to obtain for most proteins and especially for membrane proteins. An alternative is to grow two-dimensional (2D) crystals by adsorbing proteins to ligand-lipid monolayers at the surface of water. This confined geometry requires only small amounts of material and offers numerous advantages: self-assembly and ordering over micrometer scales is easier to obtain in two dimensions; although fully hydrated, the crystals are sufficiently rigid to be investigated by various techniques, such as electron crystallography or micromechanical measurements. Here we report structural studies, using grazing incidence synchrotron x-ray diffraction, of three different 2D protein crystals at the air-water interface, namely streptavidine, annexin V, and the transcription factor HupR. Using a set-up of high angular resolution, we observe narrow Bragg reflections showing long-range crystalline order in two dimensions. In the case of streptavidin the angular range of the observed diffraction corresponds to a resolution of 10 A in plane and 14 A normal to the plane. We show that this approach is complementary to electron crystallography but without the need for transfer of the monolayer onto a grid. Moreover, as the 2D crystals are accessible from the buffer solution, the formation and structure of protein complexes can be investigated in situ.
 ...
PMID:Synchrotron radiation diffraction from two-dimensional protein crystals at the air/water interface. 1086 75

Thalidomide has significant immunomodulatory properties and has been used successfully in the treatment of oral ulcers and wasting in HIV patients. However, its use is limited by its poor bioavailability due to low solubility and short half life in solution, and teratogenic and neurotoxic side-effects. Recently, water-soluble analogues of thalidomide with significantly greater immunomodulatory activity and reduced side-effects have become available. We examined the effect of thalidomide and one analogue, CC-3052, on neutrophil apoptosis following culture for 20 h in vitro. Apoptosis was assessed by reduced CD16 expression and Annexin V binding using flow cytometry. Thalidomide or CC-3052 alone had no effect on neutrophil apoptosis when used at physiological levels. However, when used together with prostaglandin E2 (10-7 M), a potent adenylate cyclase activator, CC-3052 but not thalidomide (both 10-5 M) reduced apoptosis in neutrophils from normal and HIV+ donors. The reduced apoptosis could not be attributed to the ability of CC-3052 to reduce tumour necrosis factor-alpha (TNF-alpha) production, but may be due to its PDE4 inhibitor properties, as it increased [cAMP]i, and mimicked the effect of increasing [cAMP]i using dibutryl cAMP, a membrane-permeable analogue of cAMP. The results suggest a role for thalidomide analogue CC-3052 in reducing persistent activation of the TNF-alpha system in HIV without markedly impairing neutrophil viability.
 ...
PMID:Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosis in vitro. 1097 13

Water-soluble chitosan oligomer (WSCO) has been reported to have anticancer activity, immuno-enhancing effect and antimicrobial activity. However, other biological activities are unknown. Herein, we have shown that WSCO is able to inhibit proliferation of human leukemia HL-60 cells and induce these cells to differentiate. Treatment with WSCO for 4 days resulted in a concentration-dependent reduction in HL-60 cell growth as measured by cell counting and MTT assay. This effect was accompanied by a marked increase in the proportion of G(0)/G(1) cells as measured by flow cytometry. WSCO also induced differentiation of the cells as measured by phorbol ester-dependent reduction of NBT, morphological changes as examined by Wright-Giemsa staining and expression of CD11b but not of CD14 as analysed by flow cytometry, indicating differentiation of HL-60 cells toward granulocyte-like cells. A combination of low dose of WSCO with all-trans retinoic acid, a differentiating agent toward granulocyte-like cells, exhibited a synergistic effect on the differentiation. In addition, treatment of HL-60 cells with WSCO for 6 or 8 days resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis and quantitatively by Annexin V technique using flow cytometry. Collectively, there is a potential for WSCO in the treatment of myeloid leukemia.
 ...
PMID:Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer. 1124 31

Arsenicals are toxicants and carcinogens to which large numbers of people risk exposure by contaminated water, air pollution or industrial contact. Several animal studies have determined that inorganic arsenicals are immunotoxic, but the mechanism of immune suppression is not clear. In this study, we show that trivalent arsenic inhibits enzymatic activity of the lysosomal protease cathepsin L (CathL) in the murine antigen-presenting B cell line TA3. CathL plays an important role in antigen processing, the mechanism by which antigen-presenting cells cleave foreign protein antigens to peptides for stimulating a T cell response. Deficient proteolysis may lead to diminished immune responses. Arsenite suppressed enzymatic activity within TA3 cells after 4 h exposure without affecting cell viability. Kinetic analyses revealed that the chemical was a reversible, partially noncompetitive inhibitor of CathL with a Ki of 120 microM. However, an 18 h arsenite exposure triggered massive cell death at concentrations that were substantially lower than those required for enzymatic inhibition. Morphological analysis and annexin V staining showed that arsenite-exposed TA3 cells underwent apoptosis within 18 h, and early stages of apoptosis began by 4 h. These findings suggest that apoptosis may be an important mechanism for arsenic-induced immunosuppression.
 ...
PMID:Immunosuppression by arsenic: a comparison of cathepsin L inhibition and apoptosis. 1135 77

Chronic ingestion of arsenite-contaminated drinking water causes skin, bladder, and liver cancer. The mechanism of arsenite-induced carcinogenesis is unknown. Arsenite is known to disrupt mitosis and to delay transit through M phase in normal diploid fibroblasts. SV40-transformed human fibroblasts were observed to be hypersensitive to the cytotoxic and cytostatic effects of NaAsO(2) compared with normal diploid fibroblasts in concentration-response experiments. Five to 20 microM NaAsO(2) induced cytostasis in cycling normal diploid fibroblasts but not overt lethality in quiescent normal diploid fibroblasts. High concentrations of arsenite were overtly lethal in both cycling and quiescent cells. The IC50 for cycling SV40-transformed fibroblasts was 3.8 and 4.8 microM for the SV40-transformed lines GM4429 and GM0637, respectively, whereas, in cycling normal diploid fibroblasts (GM0024), the IC50 was 24.7 microM. Microscopic examination of NaAsO(2)-treated SV40-transformed fibroblasts suggested a concentration-dependent accumulation of cells in mitosis undergoing apoptosis. Treatment of SV40-transformed fibroblasts with 0-10 microM NaAsO(2) caused a concentration-dependent inhibition of cell proliferation, accumulation of cells having G2/M DNA contents, and increases in the mitotic index. Phase microscopy, annexin V binding, and electron microscopy demonstrated that arrested mitotic cells underwent apoptosis. These results indicate that SV40-transformation sensitizes cells to arsenite-induced mitotic arrest and induction of apoptosis in the mitotic cells.
 ...
PMID:Arsenite disrupts mitosis and induces apoptosis in SV40-transformed human skin fibroblasts. 1196 75

Lipopolysaccharide (LPS) from gram-negative bacteria circulates in acute, subacute, and chronic conditions. It was hypothesized that LPS directly induces cardiac apoptosis. In adult rat ventricular myocytes (isolated with depyrogenated digestive enzymes to minimize tolerance), LPS (10 ng/ml) decreased the ratio of Bcl-2 to Bax at 12 h; increased caspase-3 activity at 16 h; and increased annexin V, propidium iodide, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining at 24 h. Apoptosis was blocked by the caspase inhibitor benzyloxycarbonyl-valine-alanine-aspartate fluoromethylketone (Z-VAD-fmk), captopril, and angiotensin II type 1 receptor (AT(1)) inhibitor (losartan), but not by inhibitors of AT(2) receptors (PD-123319), tumor necrosis factor-alpha (TNFRII:Fc), or nitric oxide (N(G)-monomethyl-L-arginine). Angiotensin II (100 nmol/l) induced apoptosis similar to LPS without additive effects. LPS in vivo (1 mg/kg iv) increased apoptosis in left ventricular myocytes for 1-3 days, which dissipated after 1-2 wk. Losartan (23 mg. kg(-1). day(-1) in drinking water for 3 days) blocked LPS-induced in vivo apoptosis. In conclusion, low levels of LPS induce cardiac apoptosis in vitro and in vivo by activating AT(1) receptors in myocytes.
 ...
PMID:Lipopolysaccharide induces apoptosis in adult rat ventricular myocytes via cardiac AT(1) receptors. 1212 89

The biochemical and physiological processes involved in apoptosis were described from the perspective of detection by standard, clinical, noninvasive imaging modalities. The difficulties of monitoring apoptosis in vivo were discussed. Magnetic resonance imaging (MRI) approaches used to study apoptosis were surveyed. The cell shrinkage associated with apoptosis can be detected due to changes in tissue water T(2) and T(1)rho relaxation times and apparent diffusion coefficient (ADC). Magnetic resonance spectroscopy (MRS) approaches used to study apoptosis in vivo have largely centered on the formation of cytoplasmic lipid bodies, detected by 1H MRS, and metabolic/bioenergetic changes detected by 31P and 13C MRS. The most successful approach to in vivo mapping of apoptosis uses the high specific binding of annexin V or synaptotagmin I to phosphatidylserine (PS) that appears on the extracellular plasma membrane of cells during apoptosis. Technetium-99m (99mTc)-radiolabeling of the annexin V and superparamagnetic iron oxide (SPIO) labeling of the C2 domain of synaptotagmin I allow good in vivo apoptosis detection by gamma camera imaging and MRI, respectively.
 ...
PMID:In vivo monitoring of apoptosis. 1265 70

Heme oxygenase-1 (HO-1), an inducible enzyme that catalyzes oxidative degradation of heme to form biliverdin, carbon monoxide and free iron, may protect tumor cells against oxidative stress, thus contributing to rapid tumor growth in vivo. Here, we discuss whether pegylated zinc protoporphyrin (PEG-ZnPP), a potent HO inhibitor, modulates the chemotherapeutic response of tumor cells to treatment that generates reactive oxygen species (ROS). PEG-ZnPP is a water-soluble HO inhibitor that accumulates in tumor tissues after intravenous administration. Cytotoxicity of antitumor agents in vitro was determined by means of MTT and annexin V assays using human colon carcinoma SW480 cells. Mice bearing sarcoma 180 tumors were used as an in vivo model. Pegylated D-amino acid oxidase (PEG-DAO), which behaves as an oxidative chemotherapeutic agent by generating toxic oxidants at tumor tissues, was administered with its substrate D-proline to mice with or without PEG-ZnPP pretreatment. PEG-ZnPP-treated SW480 cells became vulnerable to insults caused by various cytotoxic agents; the 50% lethal doses were reduced by 25%, 39%, 83%, and 61% for hydrogen peroxide, t-butyl hydroperoxide, camptothecin and doxorubicin, respectively. Cells treated with PEG-ZnPP plus cytotoxic oxidants exhibited marked production of intracellular ROS, which paralleled the incidence of apoptosis. PEG-ZnPP pretreatment significantly reduced tumor growth in mice receiving PEG-DAO/D-proline compared to no PEG-ZnPP pretreatment. These findings suggest that HO-1 may become an attractive target for chemotherapeutic intervention. Further study of the effect of PEG-ZnPP plus conventional anticancer drugs that generate ROS, such as cisplatin, camptothecin, doxorubicin, mitomycin C and etoposide, is warranted.
 ...
PMID:Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin. 1473 61


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