Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inorganic pyrophosphate promoted the acidification of an intracellular compartment in permeabilized procyclic trypomastigotes of Trypanosoma brucei, as measured by acridine orange uptake. The proton gradient generated by pyrophosphate was collapsed by addition of nigericin or NH(4)Cl. Pyrophosphate-driven proton translocation was stimulated by potassium ions and inhibited by KF, by the pyrophosphate analogs imidodiphosphate and aminomethylenediphosphonate (AMDP), and by the thiol reagent p-hydroxymercuribenzoate at concentrations similar to those that inhibit the plant vacuolar H(+)-pyrophosphatase (PPase). The proton translocation activity had a pH optimum around 7.5 and was partially inhibited by 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (10 microM) and unaffected by bafilomycin A(1) (40 nM), concanamycin A (5 nM), sodium o-vanadate (500 microM), oligomycin (1 microM), N-ethylmaleimide (100 microM), and KNO(3). AMDP-sensitive pyrophosphate hydrolysis was detected in both procyclic and bloodstream trypomastigotes. Measurements of acridine orange uptake in permeabilized procyclic trypomastigotes in the presence of different substrates and inhibitors suggested the presence of H(+)-ATPase, H(+)-PPase, and (ADP-dependent) H(+)/Na(+) antiport activity in the same compartment. Separation of bloodstream and procyclic trypomastigote extracts on Percoll gradients yielded fractions that contained H(+)-PPase (both stages) and H(+)/Na(+) exchanger (procyclics) activities but lacked markers for mitochondria, glycosomes, and lysosomes. The organelles in these fractions were identified by electron microscopy and X-ray microanalysis as acidocalcisomes (electron-dense vacuoles). These results provide further evidence for the unique nature of acidocalcisomes in comparison with other, previously described, organelles.
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PMID:Characterization of a vacuolar pyrophosphatase in Trypanosoma brucei and its localization to acidocalcisomes. 1052 60

We describe a technique for the treatment of malignant brain tumors based on local delivery of the anti-angiogenic protein endostatin from genetically engineered cells encapsulated in ultrapure sodium alginate. Alginate consists of L-guluronic and D-mannuronic acid, which in the presence of divalent cations forms an extended gel network, in which cells reside and remain immunoisolated, when implanted into the rat brain. Here, we show that endostatin-transfected cells encapsulated in alginate maintain endostatin secretion for at least four months after intracerebral implantation in rats. During the implantation period 70% of the encapsulated cells remained viable, as opposed to 85% in in vitro-cultured capsules. Rats that received transplants of BT4C glioma cells, together with endostatin-producing capsules (0.2 microg/ml per capsule), survived 84% longer than the controls. The endostatin released from the capsules led to an induction of apoptosis, hypoxia, and large necrotic avascular areas within 77% of the treated tumors, whereas all the controls were negative. The encapsulation technique may be used for many different cell lines engineered to potentially interfere with the complex microenvironment in which tumor and normal cells reside. The present work may thus provide the basis for new therapeutic approaches toward brain tumors.
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PMID:Local endostatin treatment of gliomas administered by microencapsulated producer cells. 1113 44

The current study describes new, antivascular, and antitumor effects of human endostatin. A novel system for continuous, localized delivery of antiangiogenic compounds to brain tumors was used. The delivery system was composed of endostatin-producing 293 cells encapsulated into immuno-isolating sodium alginate. Intravital multifluorescence microscopy was used to assess vascular and antitumor effects of endostatin in C6 glioma spheroids implanted into an ectopic as well as an orthotopic setting. Analysis of total and functional vascular density, microvascular diameters, vessel perfusion, tumor growth, and tumor cell migration were performed repetitively. Tumor growth was reduced by 35% in treated animals. It was of interest that tumor cell invasion into the surrounding tissue was also inhibited. The total vascular density was reduced by 67.6%, perfusion by 67%, and vessel diameters by 37%. This resulted in a significant reduction in tumor perfusion, although the vessel permeability was not influenced. We have demonstrated that human endostatin not only reduces total vascular density, as shown previously, but also greatly reduces the functionality and the diameters of the vessels. Furthermore, we show that this therapeutic approach also inhibits tumor cell invasion, thus supporting the hypothesis that tumor angiogenesis and invasion represent two interrelated processes. Finally, this work further confirms the new therapeutic concept using alginate cell-encapsulation technology for the localized delivery of therapeutic compounds to central nervous system malignancies.
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PMID:Intravital microscopy reveals novel antivascular and antitumor effects of endostatin delivered locally by alginate-encapsulated cells. 1155 58

Evidence is presented that nitric oxide (NO) may regulate blood pressure in cephalopod molluscs. In vitro tests performed on the cephalic aorta of Sepia officinalis (L.) (Cephalopoda) showed that the NO releasers (glyceroltrinitrate, sodium nitroprusside, 3-morpholinylsydnoneimine chloride and KNO(2)) induced concentration-dependent vasodilatation of vessel segments (without the tunica adventitia/periadventitia) precontracted by dopamine. These vasodilatatory actions could be totally blocked by oxadiazolo[4,3-a] quinoxalin-1-one, an inhibitor of the NO-sensitive guanylyl cyclase, and partially mimicked by the cyclic guanosine monophosphate (cGMP) analogue 8-bromo cGMP and by the phosphodiesterase inhibitor, zaprinast. The NO-precursor, L-arginine, showed vasodilatatory effects only on segments of the aorta in which the layers containing nerves (tunica adventitia/periadventitia) had been left intact, suggesting that NO synthase may be located within peripheral nerves.
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PMID:Nitric oxide: a vasodilatatory mediator in the cephalic aorta of Sepia officinalis (L.) (Cephalopoda). 1249 Oct 69

A catalogue of proteins in the human vitreous humor may contribute to elucidating the pathogenesis of various diseases in ophthalmology. To improve the recovery of proteins in vitreous, we applied one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-PAGE). Proteins were extracted from unstained gel strips and digested in gel with trypsin and the peptides were analyzed by capillary-column reversed-phase high-performance liquid chromatography coupled with electrospray ionization-ion trap-mass spectrometry. From a patient with diabetic retinopathy, 84 different proteins were identified. Most of the proteins which we identified in vitreous previously using 2D-PAGE were also identified in the present study. In total, we identified 121 different proteins including five proteins seen at the genomic level only. Four angiogenic factors, insulin-like growth factor, vascular endothelial growth factor, fibroblast growth factor, and placental endothelial cell growth factor, and three anti-angiogenic factors, pigment epithelium-derived factor, endostatin, and thrombospondin, were found, and this may contribute to elucidating the pathological changes in the concentration and the modified structures of these proteins, in diseases of the retina, especially, diabetic retinopathy.
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PMID:Catalogue of soluble proteins in human vitreous humor by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray ionization mass spectrometry including seven angiogenesis-regulating factors. 1282 93

Endostatin is a 20 kDa carboxyl-terminal fragment of collagen XVIII that, when added exogenously, inhibits endothelial proliferation and migration in vitro and angiogenesis and tumor growth in vivo. Previous results showed endostatin/collagen XVIII labeling in few endothelial cells in human glioblastoma multiforme. We have now observed constitutive release of endostatin from one of four endothelial cell lines. Induction of endostatin release was observed after H2O2, an in vitro model of cell stress, CoCl2, a model of hypoxia, and by IFN-gamma challenge. Endostatin expression and release was reduced by the nitric oxide synthase inhibitors aminoguanidine and L-NAME and induced by the NO synthase-independent NO donors sodium nitroprusside (SNP) and spermine-NONO-ate. SNP-mediated endostatin induction was abrogated by the soluble guanylate cyclase inhibitor 1H-(1.2.4) oxadiazolo (4,3-A) quinoxalin-1-one. Adenoviral endostatin transduction resulted in the release of endostatin from endothelial cells and in down-regulation of iNOS (NOS2) and eNOS (NOS3), and surprisingly in a 10% induction of PCNA. These results describe the modulation of endostatin release by the NO signaling cascade and provide important new pharmacological information for the systemic induction of endogenous endostatin release by common NO donor pharmacotherapy.
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PMID:Endothelial endostatin release is induced by general cell stress and modulated by the nitric oxide/cGMP pathway. 1283 91

The existing evidence for the nature of the phase diagram for the binary system sodium nitrate-potassium nitrate is reviewed and in particular whether the system is of the continuous solid solution type, as has often been stated in the last 80 years, or whether this system is of the eutectic type as was earlier believed and has again been asserted recently. Additional evidence from Raman spectroscopy and Raman mapping on the 50 : 50 mol%(minimum melting point) composition is now presented, supporting the eutectic classification. Abrupt changes in wavenumber, or in the wavenumber-temperature gradient of five Raman bands indicate a solid-state transition at about 115 degrees C and are attributed to a phase transition in KNO(3)-rich areas. On a fast cooled sample, Raman bands attributed to sodium nitrate-rich and potassium nitrate-rich areas were found to persist up to and slightly beyond the melting point, and although their wavenumber-positions converged, the apparent single band could still be resolved into the two bands which could be attributed to the Na-rich and K-rich areas. On cooling, the reverse change took place quickly. Measurements with the initially slow cooled sample, where these areas were bigger, showed that the spectral bands reverted to the room-temperature wavenumber values, after holding at 22 degrees C for only 60-90 min.
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PMID:The NaNO(3)/KNO(3) system: the position of the solidus and sub-solidus. 1527 11

A ditopic, macrobicyclic receptor with adjacent anion and cation binding sites is able to extract a range of monovalent salts into chloroform solution. The structures of the receptor complexed with KAcO, LiNO(3), NaNO(3), KNO(3), and NaNO(2) are characterized in solution by NMR spectroscopy and in the solid state by X-ray crystallography. The sodium and potassium salts are bound to the receptor as contact ion-pairs, with the metal cation located in the receptor's crown ether ring and the trigonal oxyanion hydrogen bonded to the receptor NH residues. The solid-state structure of the LiNO(3) complex has a bridging water molecule between the cation and anion. In all solid-state structures, the trigonal oxyanion is not located symmetrically inside the receptor cavity. It appears that anion orientation is controlled by a complex interplay of steric factors, coordination bonding to the metal cation, and hydrogen bonding with the receptor NH residues. An important feature with this latter effect is the fact that hydrogen bonds directed toward the oxygen lone pairs on a trigonal oxyanion are stronger than hydrogen bonds to the pi-electrons. In solution, the (1)H NMR spectra of the nitrate and nitrite salt complexes are noteworthy because several receptor signals, including the NH protons, undergo unusual upfield movements in chemical shift upon complexation. This is a reflection of the diamagnetic anisotropy of these trigonal oxyanions. The magnetic shielding surface for the NO(3)(-) anion is calculated using density functional theory and shown to have a shielding region directly above the central nitrogen.
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PMID:Molecular recognition of trigonal oxyanions using a ditopic salt receptor: evidence for anisotropic shielding surface around nitrate anion. 1574 Jan 28

Uptake and release of abscisic acid (AbA) by isolated mesophyll cells of Papaver somniferum is characterized by the following observations: (a) Uptake rate is a linear function of the external AbA concentration in the range from 10(-6) to 5 x 10(-5) molar, and decreases with increasing pH. At any pH, uptake rate is linearly related to the concentration of undissociated abscisic acid, calculated from the pK = 4.7 according to the Henderson-Hasselbalch equation. At low external pH (5.0), AbA accumulation in the cells is about 10-fold. (b) Uptake of AbA is completely inhibited by salts such as KNO(2) or sodium acetate, which decrease the pH gradient between medium and cells. KCN or m-chlorocarbonylcyanide phenylhydrazone inhibits AbA uptake only after longer incubation periods (20-40 minutes). (c) Uptake rate as well as equilibrium concentration is significantly higher in light than in darkness. (d) At low external pH, release of AbA from preloaded cells is strongly stimulated by KNO(2). It is concluded that AbA is distributed between leaf cells and free space according to pH gradients, with the undissociated abscisic acid being the main penetrating species. Uptake and release occur via diffusion, without participation of a carrier.
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PMID:Uptake and Release of Abscisic Acid by Isolated Photoautotrophic Mesophyll Cells, Depending on pH Gradients. 1666 71

The tonoplast ATPase from corn coleoptile membranes was solubilized using a two-step procedure consisting of a pretreatment with 0.15% (w/v) deoxycholate to remove 60% of the protein, and 40 millimolar octyl-glucoside to solubilize the ATPase. During ultracentrifugation, the solublized ATPase entered a linear sucrose gradient faster than the majority of the protein, resulting in an 11-fold purification over the initial specific activity. The partially purified ATPase was almost completely inhibited by KNO(3) with an estimated K(i) of 10 millimolar. The specific activity of the KNO(3)-sensitive ATPase was increased 29-fold during purification. N,N'-Dicyclohexylcarbodiimide also completely inhibited the ATPase with half-maximal effects at a concentration of 4 micromolar. Neither vanadate nor azide inhibited enzyme activity. The purified ATPase was stimulated by Cl(-) and preferred Mg-ATP as substrate. Analysis of frations from the sucrose gradient by sodium dodecyl sulfate-polyacrylamide gel electrophoresis led to the identification of two major polypeptides at 72,000 and 62,000 daltons which were best correlated with ATPase activity. Several minor bands also appeared to copurify with enzyme activity, but were less consistent. Radiation inactivation experiments with intact membranes indicated that the functional molecular size of the tonoplast ATPase was nearly 400,000 daltons. This suggests that the ATPase is composed of several polypeptides, possibly including the 72,000- and 62,000-dalton proteins.
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PMID:Partial purification of a tonoplast ATPase from corn coleoptiles. 1666 39


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