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71.
Kazuo Ryoyama Takahiro Nomura Shinobu Nakamura 《Cancer immunology, immunotherapy : CII》1993,37(6):385-391
We examined whether inhibitors of the arachidonic acid cascade inhibited nitric oxide (NO) production, as measured by nitrite concentration, either in macrophages or by their cytosolic fractions. Nitrite production by peritoneal macrophages from mice receiving OK-432 treatment was significantly inhibited by phospholipase A2 inhibitors [dexamethasone and 4-bromophenacyl bromide (4-BPB)], lipoxygenase inhibitors [nordihydroguaiaretic acid (NDGA) and ketoconazole] and a glutathioneS-transferase (leukotrienes LTA4-LTC4) inhibitor (ethacrynic acid). However, caffeic acid and esculetin, inhibitors of 5- and 12-lipoxygenase respectively, were not inhibitory. On the other hand, indomethacin, a cyclooxygenase inhibitor, slightly inhibited whereas another inhibitor, ibuprofen, did not. Inhibition of the nitrite production by dexamethasone, 4-BPB, NDGA and ethacrynic acid was also demonstrated when the macrophages were restimulated ex vivo with OK-432 or with lipopolysaccharide. The inhibitory activity of dexamethasone, NDGA and ethacrynic acid was significantly reduced by ex vivo restimulation with OK-432, whereas that of 4-BPB was hardly affected. Furthermore, the inhibitory activity of dexamethasone, NDGA and ethacrynic acid was much higher when the macrophages were continuously exposed to the agents than when they were pulsed. Meanwhile, inhibition by 4-BPB was almost the same with either treatment. In addition, the inhibitory activity of these agents was not blocked withl-arginine, a substrate of NO synthases, or with arachidonate metabolites (LTB4, LTC4 and LTE4). Ethacrynic acid and 4-BPB, but not dexamethasone and NDGA, also inhibited nitrite production by the cytosolic fractions from OK-432-restimulated peritoneal macrophages, and the inhibitory activity of 4-BPB was superior to that of ethacrynic acid. These agents, however, did not inhibit nitrite production from sodium nitroprusside, a spontaneous NO-releasing compound. These results indicate that dexamethasone, 4-BPB, NDGA and ethacrynic acid inhibited the production of NO by macrophages through at least two different mechanisms: one was inhibited by dexamethasone, NDGA and ethacrynic acid and the other by 4-BPB. Furthermore, 4-BPB and ethacrynic acid directly inhibited the activity of the NO synthase in macrophages, suggesting that the agents work by binding to the active site(s) of the enzyme. 相似文献
72.
Antibiotic production by strains of Gliocladium virens and its relation to the biocontrol of cotton seedling diseases 总被引:1,自引:0,他引:1
Strains of the fungal antagonist Gliocladium virens were separated into two distinct groups on the basis of secondary metabolite production in vitro. Strains of the ‘P’ group produced the antibiotics gliovirin and heptelidic acid but not the antibiotic gliotoxin and its companion, dimethylgliotoxin. Strains of the ‘Q’ group produced gliotoxin and dimethylgliotoxin but not gliovirin or heptelidic acid. Strains from both groups produced the antibiotic viridin and phytotoxin viridiol. Gliovirin was very inhibitory to Pythium ultimum but had no activity against Rhizoctonia solani, and strains that produce it were more effective seed treatment biocontrol agents of disease incited by P. ultimum. Conversely, gliotoxin was more active against R. solani than against P. ultimum, and strains that produced it were more effective seed treatments for controlling disease incited by R. solani. These results indicate that the antibiotic profiles of strains should be considered when screening strains for biocontrol efficacy, and that it may be necessary to treat seeds with a combination of strains in order to broaden the disease control spectrum. 相似文献
73.
Yonglan Liu Mingzhen Zhang Hyunbum Jang Ruth Nussinov 《Protein science : a publication of the Protein Society》2023,32(1):e4504
Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer–dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer–dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors. 相似文献
74.
Doan Minh Sang Ik Ho Na Dr. Duong Tien Anh Do Thi Mai Dung Nguyen Thi Thu Hang Nguyen T. Phuong-Anh Assoc. Prof. Dr. Pham-The Hai Assoc. Prof. Dr. Dao Thi Kim Oanh Dr. Truong Thanh Tung Soo Jung Lee Joo Hee Kwon Prof. Dr. Jong Soon Kang Prof. Dr. Sang-Bae Han Assoc. Prof. Dr. Dinh Thi Thanh Hai Prof. Dr. Nguyen-Hai Nam 《化学与生物多样性》2023,20(5):e202201030
Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity. 相似文献
75.
Han Tian Jin-Lin Yang Yirui Deng Wenhao Tang Ruiping Liu Chenyang Xu Peng Han Hong Jin Fan 《Liver Transplantation》2023,13(1):2202603
The progress of aqueous zinc batteries (AZBs) is limited by the poor cycling life due to Zn anode instability, including dendrite growth, surface corrosion, and passivation. Inspired by the anti-corrosion strategy of steel industry, a compounding corrosion inhibitor (CCI) is employed as the electrolyte additive for Zn metal anode protection. It is shown that CCI can spontaneously generate a uniform and ≈30 nm thick solid-electrolyte interphase (SEI) layer on Zn anode with a strong adhesion via Zn O bonding. This SEI layer efficiently prohibits water corrosion and guides homogeneous Zn deposition without obvious dendrite formation. This enables reversible Zn deposition and dissolution for over 1100 h under the condition of 1 mA cm−2 and 1 mAh cm−2 in symmetric cells. The Zn-MnO2 full cells with CCI-modified electrolyte deliver an ultralow capacity decay rate (0.013% per cycle) at 0.5 A g−1 over 1000 cycles. Such an innovative strategy paves a low-cost way to achieve AZBs with long lifespan. 相似文献
76.
Vassilios Tsikaris 《Journal of peptide science》2004,10(10):589-602
Activation of the platelet surface receptor GPIIb/IIIa is the final pathway of platelet aggregation, regardless of the initiating stimulus. RGD analogues, peptidomimetics and monoclonal antibodies to GPIIb/IIIa have been developed targeting the blockage of the receptor and inhibition of the fibrinogen binding. However, the intrinsic activating effect of GPIIb/IIIa blockers is widely discussed as one potential contributing factor for the disappointing outcome of trials with GPIIb/IIIa inhibitors. An alternative method for thrombus prevention could be the use of specific fibrinogen blockers since they will act at the final step of the platelet aggregation and are expected to leave the receptor unaffected. To achieve this target the design of the fibrinogen ligands could be based on (i) sequences derived from GPIIb/IIIa ligand binding sites, and (ii) sequences complementary to RGD and/or to fibrinogen gamma-chain. The available information, which could be used as a starting point for developing potent fibrinogen ligands, is reviewed. 相似文献
77.
Sarrah M'Barek Ziad Fajloun Sandrine Cestle Christiane Devaux Pascal Mansuelle Amor Mosbah Besma Jouirou Massimo Mantegazza Jurphaas van Rietschoten Mohamed El Ayeb Herv Rochat Jean‐Marc Sabatier Francois Sampieri 《Journal of peptide science》2004,10(11):666-677
Aah I is a 63-residue alpha-toxin isolated from the venom of the Buthidae scorpion Androctonus australis hector, which is considered to be the most dangerous species. We report here the first chemical synthesis of Aah I by the solid-phase method, using a Fmoc strategy. The synthetic toxin I (sAah I) was renatured in DMSO-Tris buffer, purified and subjected to thorough analysis and comparison with the natural toxin. The sAah I showed physico-chemical (CD spectrum, molecular mass, HPLC elution), biochemical (amino-acid composition, sequence), immunochemical and pharmacological properties similar to those of the natural toxin. The synthetic toxin was recognized by a conformation-dependent monoclonal anti-Aah I antibody, with an IC50 value close to that for the natural toxin. Following intracerebroventricular injection, the synthetic and the natural toxins were similarly lethal to mice. In voltage-clamp experiments, Na(v) 1.2 sodium channel inactivation was inhibited by the application of sAah I or of the natural toxin in a similar way. This work describes a simple protocol for the chemical synthesis of a scorpion alpha-toxin, making it possible to produce structural analogues in time. 相似文献
78.
C. Marjorie Aelion J. N. Shaw R. P. Ray M. A. Widdowson H. W. Reeves 《Soil & Sediment Contamination》1996,5(3):225-241
Portable meters and simplified gas Chromatographic (GC) techniques were investigated for monitoring volatile hydrocarbon (HC), CO2, and O2, concentrations in groundwater, exhaust gases, and soil vapor during in situ remediation using soil vapor extraction (SVE) and air sparging (AS). Results of groundwater samples analyzed in‐house using a headspace technique compared well to split samples analyzed by a certified analytical laboratory (r2 = 0.94). SVE exhaust gas HC and CO2 concentrations measured using a GT201 portable HC/O2 meter and a RA‐411A meter (GasTech), respectively, were highly correlated with in‐house laboratory GC analyses (r2 = 0.91). O2 concentrations fell in a small range and meter analyses were not well correlated with laboratory analyses. Results of soil gas monitoring were not as well correlated as those for exhaust gases for HC, CO2, or O2, perhaps due to environmental conditions such as changes in relative humidity or the wider range of soil gas values. Overall, the meters were good indicators of vapor contamination, they greatly simplified estimates of total HC mass removal, and they allowed estimates of the biological contribution to contaminant removal during the remediation process. 相似文献
79.
R E Moore 《Journal of industrial microbiology & biotechnology》1996,16(2):134-143
An elaborate array of structurally-novel and biologically-active cyclic peptides and depsipeptides are found in blue-green algae (cyanobacteria). Several of these compounds possess structures that are similar to those of natural products from marine invertebrates. Most of these cyclic peptides and depsipeptides, such as the microcystins and the lyngbyatoxins, will probably only be useful as biochemical research tools. A few, however, have the potential for development into useful commercial products. For example, cryptophycin-1, a novel inhibitor of microtubule assembly fromNostoc sp GSV 224, shows impressive activity against a broad spectrum of solid tumors implanted in mice, including multidrug-resistant ones, and majusculamide C, a microfilament-depolymerizing agent fromLyngbya majuscula, shows potent fungicidal activity and may have use in the treatment of resistant fungal-induced diseases of domestic plants and agricultural crops. 相似文献
80.
During the production by mammalian cells of recombinant factor VIII from which the B domain was deleted (rFVIII), proteolytic
cleavages in the C-terminal part of the heavy chain were observed (Kjalke et al., 1995). By radioactive pulse labelling it
was investigated whether the cleavages took place inside the cells during protein synthesis or after release in the medium.
The rFVIII-producing CHO (Chinese hamster ovary) cells were cultured in the presence of 35S-methionine and then the cell lysate and the conditioned media were immunoprecipitated and analyzed by electrophoresis. By
pulse labelling and chasing for various time periods, it was shown that the cleavages only took place after secretion of the
protein from the cells. Adding cell lysate to uncleaved rFVIII caused cleavage of the heavy chain, as seen by loss of binding
to a monoclonal antibody specific for intact rFVIII, indicating that the cleavage was performed by proteinase(s) released
from the lysed cells. By incubating intact rFVIII with the multicatalytic proteinase (proteasome) present in cytoplasm and
nucleus of eukaryotic cells, loss of binding to the monoclonal antibody was observed. This indicates that the multicatalytic
proteinase, released from lysed rFVIII producing cells, could be responsible for the cleavage of rFVIII. Among several protease
inhibitors tested, only bacitracin was found to diminish the extent of cleavage. Phosphatidylserine also protected rFVIII
against cleavage, probably by binding to rFVIII.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献