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71.
Cascone T Morelli MP Morgillo F Kim WY Rodolico G Pepe S Tortora G Berrino L Lee HY Heymach JV Ciardiello F 《Journal of cellular physiology》2008,216(3):698-707
The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt. 相似文献
72.
Annelene Pengerud Marie-France Dignac Giacomo Certini Line Tau Strand Claudia Forte Daniel P. Rasse 《Biogeochemistry》2017,135(3):277-292
Increased mineralization of the organic matter (OM) stored in permafrost is expected to constitute the largest additional global warming potential from terrestrial ecosystems exposed to a warmer climate. Chemical composition of permafrost OM is thought to be a key factor controlling the sensitivity of decomposition to warming. Our objective was to characterise OM from permafrost soils of the European Arctic: two mineral soils—Adventdalen, Svalbard, Norway and Vorkuta, northwest Russia—and a “palsa” (ice-cored peat mound patterning in heterogeneous permafrost landscapes) soil in Neiden, northern Norway, in terms of molecular composition and state of decomposition. At all sites, the OM stored in the permafrost was at an advanced stage of decomposition, although somewhat less so in the palsa peat. By comparing permafrost and active layers, we found no consistent effect of depth or permafrost on soil organic matter (SOM) chemistry across sites. The permafrost-affected palsa peat displayed better preservation of plant material in the deeper layer, as indicated by increasing contribution of lignin carbon to total carbon with depth, associated to decreasing acid (Ac) to aldehyde (Al) ratio of the syringyl (S) and vanillyl (V) units, and increasing S/V and contribution of plant-derived sugars. By contrast, in Adventdalen, the Ac/Al ratio of lignin and the Alkyl C to O-alkyl C ratio in the NMR spectra increased with depth, which suggests less oxidized SOM in the active layer compared to the permafrost layer. In Vorkuta, SOM characteristics in the permafrost profile did not change substantially with depth, probably due to mixing of soil layers by cryoturbation. The composition and state of decomposition of SOM appeared to be site-specific, in particular bound to the prevailing organic or mineral nature of soil when attempting to predict the SOM proneness to degradation. The occurrence of processes such as palsa formation in organic soils and cryoturbation should be considered when up-scaling and predicting the responses of OM to climate change in arctic soils. 相似文献
73.
Franco Chimenti Daniela Secci Adriana Bolasco Paola Chimenti Arianna Granese Simone Carradori Elias Maccioni M. Cristina Cardia Matilde Yáñez Francisco Orallo Stefano Alcaro Francesco Ortuso Roberto Cirilli Rosella Ferretti Simona Distinto Johannes Kirchmair Thierry Langer 《Bioorganic & medicinal chemistry》2010,18(14):5063-5070
The present study reports on synthesis in high yields (70–99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1–45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds. 相似文献
74.
Acid secretion and membrane reorganization in single gastric parietal cell in primary culture 总被引:1,自引:0,他引:1
P Mangeat T Gusdinar A Sahuquet D K Hanzel J G Forte R Magous 《Biology of the cell / under the auspices of the European Cell Biology Organization》1990,69(3):223-231
A digitally-enhanced videomicroscopy study of rabbit gastric parietal cells in primary culture was performed using alternate observations with differential interference contrast and fluorescence optics of cells mounted and perfused on a temperature-controlled microscope stage. The effect of histamine, a physiological effector of acid secretion, was followed. Isolated parietal cells possess an internal apical vacuole, which kept the cell in a pseudopolarized state. This apical vacuole is a site of acid secretion. This was demonstrated by the direct visualization of the uptake of the fluorescent weak base 9-amino acridine and of the concomitant enormous swelling of the acid vacuole which reached an estimated size of 3-7 times the normal cell volume. This morphological change of shape and acidification of apical vacuoles was fully reversible and cells could respond to successive stimulations. A quantitative study of these events provided a value of the acid accumulation index for each single cell in response to histamine. Individual cell response varied within a factor of 7. The cellular localization of the proton pump complex responsible for acid secretion and of the major components of the secretory microvilli, actin and ezrin, a histamine-dependent phosphorylation target of protein kinase A, were detected by indirect immunofluorescence microscopy in resting and stimulated cells. Both actin and ezrin colocalized at the apical vacuole membrane in resting and stimulated cells, whereas the proton pump shifted from an intracytoplasmic pool to the apical vacuole membrane upon stimulation. 相似文献
75.
Daniel S. Maynard J. Timothy Wootton Carlos A. Servn Stefano Allesina 《Ecology letters》2019,22(6):1028-1037
Coexistence in ecological communities is governed largely by the nature and intensity of species interactions. Countless studies have proposed methods to infer these interactions from empirical data, yet models parameterised using such data often fail to recover observed coexistence patterns. Here, we propose a method to reconcile empirical parameterisations of community dynamics with species‐abundance data, ensuring that the predicted equilibrium is consistent with the observed abundance distribution. To illustrate the approach, we explore two case studies: an experimental freshwater algal community and a long‐term time series of displacement in an intertidal community. We demonstrate how our method helps recover observed coexistence patterns, capture the core dynamics of the system, and, in the latter case, predict the impacts of experimental extinctions. Collectively, these results demonstrate an intuitive approach for reconciling observed and empirical data, improving our ability to explore the links between species interactions and coexistence in natural systems. 相似文献
76.
The dynamic evolution of the PrP(C) from its NMR-derived conformation to a beta-sheet-rich, aggregation-prone conformation is studied through all-atom, explicit solvent molecular dynamics in different temperature and pH conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach aimed at identifying the key residues for the stabilization and folding of the protein. It is shown that under native conditions the stabilization energy is concentrated in regions of the helices H1 and H3, whereas under misfolding conditions (low pH, high temperature, or mutations in selected sites) it is spread out over helix H2. Misfolding appears to be a rearrangement of the chain that disrupts most of the native secondary structure of the protein, producing some beta-rich conformations with an energy distribution similar to that of the native state. 相似文献
77.
Aquilano K Filomeni G Di Renzo L Vito Md Stefano Cd Salimei PS Ciriolo MR Marfè G 《Free radical research》2007,41(4):452-460
In this study, we found that production of both reactive oxygen (ROS) and nitrogen (RNS) species is a very early event related to treatment with hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was paralleled by the increase of the mRNA and protein level of the inducible form of the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to the failure of mitochondrial trans-membrane potential (ΔΨ), was necessary for the induction of apoptosis as demonstrated by the protection against sorbitol-mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors. The synergistic action of ROS and RNS was finally demonstrated by pre-treatment with rosmarinic acid that, by powerfully buffering both these species, prevents impairment of ΔΨ and cell death. Overall results suggest that the occurrence of apoptosis upon sorbitol treatment is an event mediated by oxidative/nitrosative stress rather than a canonical hyperosmotic shock. 相似文献
78.
79.
We examined vertical migration and colonisation patterns of stream macroinvertebrates within the substratum of an Apennine
creek in NW Italy. Macrobenthos was sampled at three depths in the streambed (0–5, 5–10, 10–15 cm) by means of artificial
baskets filled with natural substratum. We placed 42 traps (5×5×15 cm), i.e. 21 top-opened (T-traps) and 21 bottom-opened
(B-traps), each composed of three overlapping baskets (high-H, medium-M and low-L), to evaluate differences in the vertical
movements. We also collected Surber samples to compare interstitial assemblages with streambed communities. The multilevel
traps yielded 42 taxa, compared with 60 taxa in the natural riverbed. Interstitial traps were rapidly colonised; both taxa
richness and organism number increased during the 42-day study period. We found active migration in both vertical directions,
but there were more invertebrates in the top-opened traps than in the bottom-opened traps. In the T-traps the most colonised
baskets were those placed at the H level, while in the B-traps the L level baskets were more rapidly colonised. The interstitial
assemblages differed markedly from the streambed communities in both composition and functional organisation, with more collector-gatherers
and predators in the interstitial zone and more filterers and scrapers in the natural riverbed. In Apennine lotic systems,
the interstitial zone is an important habitat for stream macrobenthos, although it may not be used by all species. 相似文献
80.
Giorgia Pedini Mariachiara Buccarelli Fabrizio Bianchi Laura Pacini Giulia Cencelli Quintino Giorgio DAlessandris Maurizio Martini Stefano Giannetti Franceschina Sasso Valentina Melocchi Maria Giulia Farace Tilmann Achsel Luigi M. Larocca Lucia Ricci-Vitiani Roberto Pallini Claudia Bagni 《Cell death & disease》2022,13(8)