2,715 results on '"Cytochalasins"'
Search Results
152. Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes.
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Zhu, Hucheng, Chen, Chunmei, Tong, Qingyi, Li, Xiao ‐ Nian, Yang, Jing, Xue, Yongbo, Luo, Zengwei, Wang, Jianping, Yao, Guangmin, and Zhang, Yonghui
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ASPERGILLUS , *DIMERS , *MOIETIES (Chemistry) , *CASPASES , *CYTOCHALASINS - Abstract
Two bioactive merocytochalasans, epicochalasines A ( 1) and B ( 2), a new class of cytochalasans bearing unexpected scaffolds consisting of fused aspochalasin and epicoccine dimer moieties, were isolated from the liquid culture broth of Aspergillus flavipes. Both 1 and 2 possess a hendecacyclic 5/6/11/5/6/5/6/5/6/6/5 ring system containing an adamantyl cage and as many as 19 stereogenic centers; however, the fusion patterns of 1 and 2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of 1 and 2 were determined by X-ray diffraction and calculated ECD, respectively. The biogenetic pathways of 1 and 2 are proposed to involve Diels-Alder and nucleophilic addition reactions. Both 1 and 2 induced significant G2/M-phase cell-cycle arrest. Furthermore, we found that merocytochalasans induce apoptosis in leukemia cells through the activation of caspase-3 and the degradation of PARP. [ABSTRACT FROM AUTHOR]
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- 2016
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153. Targeting glycolysis in the malaria parasite Plasmodium falciparum.
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Niekerk, David D., Penkler, Gerald P., Toit, Francois, and Snoep, Jacky L.
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PLASMODIUM falciparum , *GLYCOLYSIS , *GLUCOSE transporters , *CYTOCHALASINS , *GLUCOKINASE , *PHOSPHOFRUCTOKINASES - Abstract
Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand. Database The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at . The SEEK-study including the experimental data set is available at DOI (). [ABSTRACT FROM AUTHOR]
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- 2016
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154. Allahabadolactones A and B from the endophytic fungus, Aspergillus allahabadii BCC45335.
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Sadorn, Karoon, Saepua, Siriporn, Boonyuen, Nattawut, Laksanacharoen, Pattiyaa, Rachtawee, Pranee, Prabpai, Samran, Kongsaeree, Palangpon, and Pittayakhajonwut, Pattama
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LACTONES , *ENDOPHYTIC fungi , *ASPERGILLUS , *ERGOSTEROL , *AMINO acids , *CYTOCHALASINS - Abstract
Two new compounds, allahabadolactones A ( 1 ) and B ( 2 ), along with 10 known compounds including 16-amino-isopimar-7-en-19-oic acid ( 3 ), 16-α- d -glucopyranosyloxyisopimar-7-en-19-oic acid ( 4 ), 16-α- d -mannopyranosyloxyisopimar-7-en-19-oic acid ( 5 ), ergosterol, (22 E )-5α,8α-epidioxyergosta-6,22-dien-3β-ol, cerevisterol, ( R )-(−)-methoxycarbonylmellein, (−)-piliformic acid, 7-dechlorogriseofulvin, and cytochalasin D, were isolated from the endophytic fungus, Aspergillus allahabadii BCC45335. Their chemical structures were determined based on NMR spectroscopic and mass spectrometric analyses. The absolute stereochemistry of compound 1 was established by an X-ray crystallographic analysis and the reactions with Mosher's reagents. A plausible biosynthesis of allahabadolactones A ( 1 ) and B ( 2 ) was also proposed. Antibacterial activity against Bacillus cereus and cytotoxicity against MCF-7, KB, NCI-H187, and Vero cells of the isolated compounds were also evaluated. [ABSTRACT FROM AUTHOR]
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- 2016
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155. Evaluation of cytochalasin B and 6-dimethylaminopurine for tetraploidy induction in the Eastern oyster, Crassostrea virginica.
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Peachey, Brittany L. and Jr.Allen, Standish K.
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AMERICAN oyster , *CYTOCHALASINS , *ADENINE , *TETRAPLOIDY , *CYTOKINES , *TOXICOLOGY of poisonous fishes , *HEALTH risk assessment - Abstract
Cytochalasin B (CB) has been used to induce tetraploidy in oysters since the practice began in 1993. However, CB is toxic and presents health risks to hatchery workers who administer the treatment. 6-dimethylaminopurine (6-DMAP) is also an effective cytokinetic inhibitor, and does not carry the health risks of CB. We examined the relative effectiveness of 6-DMAP vs CB for producing tetraploids in the Eastern oyster ( Crassostrea virginica ). Survival and yield of tetraploids varied widely among the 15 experiments. Larvae resulting from 6-DMAP treatment had higher survival in 11 of the 14 trials on day two and day six/seven. For yield of tetraploids, 10 of 13 6-DMAP treatments had higher proportions of tetraploids on day two and at the second sampling – day six, seven, or nine – 7 of 10 had higher proportions of tetraploids. Tetraploid spat were obtained from the majority of surviving cultures. Based on these results, 6-DMAP can effectively replace CB for inducing polyploidy in C. virginica , and probably other Crassostrea spp. , due to the success of the treatment, the ease of application, and the reduction in health risk to hatchery workers. This study set the precedent for the use of 6-DMAP on C. virginica and established a new procedure for inducing tetraploids using triploid eggs. It might be possible to refine the treatment to further optimize yield of tetraploids. Statement of relevance In this manuscript we report a novel method of inducing tetraploid Crassostrea virginica from triploid eggs using 6-dimethylaminopurine. We compare the efficiency of cytochalasin B and 6-dimethylaminopurine for tetraploid induction. We also report the expected fecundity of triploid C. virginica females. The method of tetraploidy induction we report here will likely be useful for inducing tetraploidy in other Crassostrea spp. [ABSTRACT FROM AUTHOR]
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- 2016
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156. Internalization of titanium dioxide nanoparticles by glial cells is given at short times and is mainly mediated by actin reorganization-dependent endocytosis.
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Huerta-García, Elizabeth, Márquez-Ramírez, Sandra Gissela, Ramos-Godinez, María del Pilar, López-Saavedra, Alejandro, Herrera, Luis Alonso, Parra, Alberto, Alfaro-Moreno, Ernesto, Gómez, Erika Olivia, and López-Marure, Rebeca
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TITANIUM dioxide nanoparticles , *NEUROGLIA , *ACTIN , *ENDOCYTOSIS , *TRANSMISSION electron microscopy , *CYTOCHALASINS - Abstract
Many nanoparticles (NPs) have toxic effects on multiple cell lines. This toxicity is assumed to be related to their accumulation within cells. However, the process of internalization of NPs has not yet been fully characterized. In this study, the cellular uptake, accumulation, and localization of titanium dioxide nanoparticles (TiO 2 NPs) in rat (C6) and human (U373) glial cells were analyzed using time-lapse microscopy (TLM) and transmission electron microscopy (TEM). Cytochalasin D (Cyt-D) was used to evaluate whether the internalization process depends of actin reorganization. To determine whether the NP uptake is mediated by phagocytosis or macropinocytosis, nitroblue tetrazolium (NBT) reduction was measured and the 5-(N-ethyl-N-isopropyl)-amiloride was used. Expression of proteins involved with endocytosis and exocytosis such as caveolin-1 (Cav-1) and cysteine string proteins (CSPs) was also determined using flow cytometry. TiO 2 NPs were taken up by both cell types, were bound to cellular membranes and were internalized at very short times after exposure (C6, 30 min; U373, 2 h). During the uptake process, the formation of pseudopodia and intracellular vesicles was observed, indicating that this process was mediated by endocytosis. No specific localization of TiO 2 NPs into particular organelles was found: in contrast, they were primarily localized into large vesicles in the cytoplasm. Internalization of TiO 2 NPs was strongly inhibited by Cyt-D in both cells and by amiloride in U373 cells; besides, the observed endocytosis was not associated with NBT reduction in either cell type, indicating that macropinocytosis is the main process of internalization in U373 cells. In addition, increases in the expression of Cav-1 protein and CSPs were observed. In conclusion, glial cells are able to internalize TiO 2 NPs by a constitutive endocytic mechanism which may be associated with their strong cytotoxic effect in these cells; therefore, TiO 2 NPs internalization and their accumulation in brain cells could be dangerous to human health. [ABSTRACT FROM AUTHOR]
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- 2015
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157. Remodelling of actin cytoskeleton in tomato cells in response to inoculation with a biocontrol strain of Fusarium oxysporum in comparison to a pathogenic strain.
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Humbert, C., Aimé, S., Alabouvette, C., Steinberg, C., and Olivain, C.
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FUSARIUM oxysporum , *CYTOPLASMIC filaments , *TOMATO disease & pest resistance , *CELL death , *CYTOCHALASINS , *POLYMERIZATION - Abstract
Knowing that actin microfilaments play a key role in the mobilization of the defence-associated cellular responses, the aim of this study was to compare changes affecting the actin cytoskeleton in tomato cells after inoculation with germinated microconidia of a biocontrol (Fo47, Fom24) or a pathogenic (Fol8) strain of Fusarium oxysporum. Actin microfilaments were observed by labelling with TRITC-phalloidin combined with fluorescence microscopy. Results showed that only tenuous changes in the actin cytoskeleton architecture occurred after inoculation with the biocontrol strains whereas the actin cytoskeleton was significantly altered after inoculation with the pathogenic one. In the two types of interaction, cell death occurs and can be considered as one key component of cell defence responses. A pharmacological approach using cytochalasins was chosen to determine whether the inhibition of actin polymerization differently affects the kinetics of tomato cell death. Data showed that cytochalasins reduced cell death induced by the biocontrol strain Fo47, and in contrast, increased cell death induced by the pathogenic strain Fol8, suggesting that the pathway leading to cell death differs in the protective and compatible interactions. [ABSTRACT FROM AUTHOR]
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- 2015
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158. Mycelial growth rate and toxin production in the seed pathogen Pyrenophora semeniperda: resource trade-offs and temporally varying selection.
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Meyer, S. E., Masi, M., Clement, S., Davis, T. L., and Beckstead, J.
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CHEATGRASS brome , *PLANT gene banks , *GERMINATION , *CYTOCHALASINS , *STROMAL cells - Abstract
Pyrenophora semeniperda, an important pathogen in Bromus tectorum seed banks in semi-arid western North America, exhibits >4-fold variation in mycelial growth rate. Host seeds exhibit seasonal changes in dormancy that affect the risk of pathogen-caused mortality. The hypothesis tested is that contrasting seed dormancy phenotypes select for contrasting strategies for increasing pathogen fitness, and that increased fitness on nondormant seeds involves a resource trade-off between toxin production and growth. The strategy for successfully attacking rapidly germinating nondormant seeds at high inoculum loads in autumn involves increased post-infection aggressiveness to prevent seed escape through germination. An earlier study demonstrated that slow-growing strains caused higher mortality than faster-growing strains on nondormant host seeds at high inoculum loads. In this study, production of the toxin cytochalasin B was significantly higher in slower-growing strains, and was induced only in seeds or in seed-constituent-containing media. Its production was reduced in vivo by Bromus tectorum seeds, suggesting direct involvement in pathogenesis on seeds. Fast-growing strains caused significantly higher mortality than slow-growing strains at low inoculum loads on dormant seeds, which apparently have resistance that is overcome at high loads or through rapid mycelial proliferation. In a co-inoculation study, the fast-growing isolate produced 3 × more stromata than the slow-growing isolate on dormant seeds, whereas the slow-growing isolate was twice as successful on nondormant seeds. These results provide evidence that mycelial growth rate variation and associated variation in cytochalasin B production represent a trade-off maintained through temporally varying selection resulting from seasonal variation in host seed dormancy status. [ABSTRACT FROM AUTHOR]
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- 2015
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159. Two new cytochalasins from an endophytic fungus, KL-1.1 isolated from Psidium guajava leaves.
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Okoye, Festus B.C., Nworu, Chukwuemeka S., Debbab, Abdessamad, Esimone, Charles O., and Proksch, Peter
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Chemical investigation of the endophytic fungus, KL-1.1, isolated from the leaves of Psidium guajava (Linn) led to the isolation of two new cytochalasin derivatives, 18-desoxy-19,20-epoxycytochalasin C and 18-desoxycytochalasin C, together with five other known derivatives. The structures of the isolated compounds were elucidated by one and two dimensional nuclear magnetic resonance spectroscopy as well as by mass spectrometry. These compounds represent novel chemical scaffold with potential for development into anticancer agents. [ABSTRACT FROM AUTHOR]
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- 2015
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160. Single cell active force generation under dynamic loading – Part I: AFM experiments.
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Weafer, P.P., Reynolds, N.H., Jarvis, S.P., and McGarry, J.P.
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DYNAMIC testing of materials ,CYTOCHALASINS ,ACTIN ,CYTOSKELETON ,TISSUE engineering - Abstract
A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Measured forces for the untreated cells are dramatically different to cytochalasin-D (cyto-D) treated cells, indicating that the contractile actin cytoskeleton plays a critical role in the response of cells to dynamic loading. Following a change in applied strain magnitude, while maintaining a constant applied strain rate, the compression force for contractile cells recovers to 88.9 ± 7.8% of the steady state force. In contrast, cyto-D cell compression forces recover to only 38.0 ± 6.7% of the steady state force. Additionally, untreated cells exhibit strongly negative (pulling) forces during unloading half-cycles when the probe is retracted. In comparison, negligible pulling forces are measured for cyto-D cells during probe retraction. The current study demonstrates that active contractile forces, generated by actin–myosin cross-bridge cycling, dominate the response of single cells to dynamic loading. Such active force generation is shown to be independent of applied strain magnitude. Passive forces generated by the applied deformation are shown to be of secondary importance, exhibiting a high dependence on applied strain magnitude, in contrast to the active forces in untreated cells. Statement of significance A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Contractile cells, which contain the active force generation machinery of the actin cytoskeleton, are shown to be insensitive to applied strain magnitude, exhibiting high resistance to dynamic compression and stretching. Such trends are not observed for cells in which the actin cytoskeleton has been chemically disrupted. These biomechanical insights have not been previously reported. This detailed characterisation of single cell active and passive stress during dynamic loading has important implications for tissue engineering strategies, where applied deformation has been reported to significantly affect cell mechanotransduction and matrix synthesis. [ABSTRACT FROM AUTHOR]
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- 2015
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161. Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins and Formal Synthesis of Trichoderone A
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Oscar Gayraud, Nicolas Casaretto, Bastien Nay, Benjamin Laroche, Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie moléculaire (LCM), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)
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Cycloaddition Reaction ,Molecular Structure ,010405 organic chemistry ,Stereochemistry ,Chemistry ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Organic Chemistry ,Total synthesis ,Substrate (chemistry) ,010402 general chemistry ,Cytochalasins ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Formal synthesis ,Biomimetics ,Cyclization ,Intramolecular force ,Stereoselectivity ,Physical and Theoretical Chemistry ,Oxidation-Reduction ,Ireland–Claisen rearrangement - Abstract
International audience; Aspochalasins are leucine-derived cytochalasins. Their complexity is often associated to a high degree of biosynthetic oxidative transformations that could inspire a two-phase strategy in total synthesis. In that context, we describe the synthesis of a putative biomimetic tetracyclic intermediate. The key constructive steps are an intramolecular Diels-Alder reaction to install the characteristic isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement made on a highly unsaturated substrate. This work also constitutes a formal synthesis of trichoderone A.
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- 2021
162. Metaphloem development in the Arabidopsis root tip
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Christian S. Hardtke and Moritz Graeff
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0106 biological sciences ,0301 basic medicine ,Meristem ,Arabidopsis ,Phloem ,Root tip ,Plant Roots ,01 natural sciences ,law.invention ,03 medical and health sciences ,Sieve ,Gene Expression Regulation, Plant ,law ,Phloem transport ,Sieve tube element ,Molecular Biology ,Ecosystem ,biology ,Arabidopsis Proteins ,Stem Cells ,Membrane Proteins ,Cell Differentiation ,biology.organism_classification ,Cytochalasins ,Stem cell niche ,Cell biology ,Gene Ontology ,030104 developmental biology ,Developmental trajectory ,010606 plant biology & botany ,Developmental Biology - Abstract
The phloem transport network is a major evolutionary innovation that enabled plants to dominate terrestrial ecosystems. In the growth apices, the meristems, apical stem cells continuously produce early ‘protophloem’. This is easily observed in Arabidopsis root meristems, in which the differentiation of individual protophloem sieve element precursors into interconnected conducting sieve tubes is laid out in a spatio-temporal gradient. The mature protophloem eventually collapses as the neighboring metaphloem takes over its function further distal from the stem cell niche. Compared with protophloem, metaphloem ontogenesis is poorly characterized, primarily because its visualization is challenging. Here, we describe the improved TetSee protocol to investigate metaphloem development in Arabidopsis root tips in combination with a set of molecular markers. We found that mature metaphloem sieve elements are only observed in the late post-meristematic root, although their specification is initiated as soon as protophloem sieve elements enucleate. Moreover, unlike protophloem sieve elements, metaphloem sieve elements only differentiate once they have fully elongated. Finally, our results suggest that metaphloem differentiation is not directly controlled by protophloem-derived cues but rather follows a distinct, robust developmental trajectory.
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- 2021
163. New Cytotoxic Cytochalasans from a Plant-Associated Fungus
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Tantan, Li, Yun, Wang, Li, Li, Mengyue, Tang, Qinghong, Meng, Cun, Zhang, Erbing, Hua, Yuehu, Pei, and Yi, Sun
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Aquatic Organisms ,endophytic fungus ,Chaetomium globosum kz-19 ,Antineoplastic Agents ,Chaetomium ,Cytochalasins ,Article ,Inhibitory Concentration 50 ,A549 Cells ,cytochalasans ,Humans ,cytotoxicity ,HeLa Cells ,Phytotherapy - Abstract
Four new cytochalasans, phychaetoglobins A–D (1–4), together with twelve known cytochalasans (5–16), were isolated from a mangrove-associated fungus Chaetomium globosum kz-19. The new structures were elucidated on the basis of extensive 1D and 2D NMR, HR ESIMS spectroscopic analyses, and electronic circular dichroism (ECD) calculations. The absolute configuration of 2 was established by application of Mosher’s method. Compounds 4–8 exhibited moderate cytotoxicities against A549 and HeLa cell lines with the IC50 values less than 20 μM.
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- 2021
164. Aspochalasin H1: A New Cyclic Aspochalasin from Hawaiian Plant-Associated Endophytic Fungus
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Mallique, Qader, K H Ahammad Uz, Zaman, Zhenquan, Hu, Cong, Wang, Xiaohua, Wu, and Shugeng, Cao
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Ovarian Neoplasms ,endophytic fungi ,Magnetic Resonance Spectroscopy ,Circular Dichroism ,Antineoplastic Agents ,Breast Neoplasms ,Boraginaceae ,Cytochalasins ,Hawaii ,Article ,Anti-Bacterial Agents ,aspochalasin ,Aspergillus ,antibacterial activity ,Cell Line, Tumor ,MCF-7 Cells ,epoxide ,Humans ,Female ,Cell Proliferation - Abstract
Aspergillus is one of the most diverse genera, and it is chemically profound and known to produce many biologically active secondary metabolites. In the present study, a new aspochalasin H1 (1), together with nine known compounds (2–10), were isolated from a Hawaiian plant-associated endophytic fungus Aspergillus sp. FT1307. The structures were elucidated using nuclear magnetic resonance (NMR) (1H, 1H-1H COSY, HSQC, HMBC, ROESY and 1D NOE), high-resolution electrospray ionization mass spectroscopy (HRESIMS), and comparisons with the reported literature. The absolute configuration of the new compound was established by electronic circular dichroism (ECD) in combination with NMR calculations. The new compound contains an epoxide moiety and an adjacent trans-diol, which has not been reported before in the aspochalasin family. The antibacterial screening of the isolated compounds was carried out against pathogenic bacteria (Staphylococcus aureus, Methicillin-resistant S. aureus and Bacillus subtilis). The antiproliferative activity of compounds 1–10 was evaluated against human breast cancer cell lines (MCF-7 and T46D) and ovarian cancer cell lines (A2780).
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- 2021
165. School of Pharmaceutical Sciences Researchers Describe Findings in Pharmaceuticals (Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic Fungus Xylaria curta E10 and Their Cytotoxicity).
- Abstract
Keywords for this news article include: School of Pharmaceutical Sciences, Wuhan, People's Republic of China, Asia, Pharmaceuticals, Mycotoxins, Cytochalasins, Biological Factors, Drugs and Therapies. Biological Factors, Cytochalasins, Drugs and Therapies, Mycotoxins, Pharmaceuticals Keywords: Biological Factors; Cytochalasins; Drugs and Therapies; Mycotoxins; Pharmaceuticals EN Biological Factors Cytochalasins Drugs and Therapies Mycotoxins Pharmaceuticals 2475 2475 1 03/23/23 20230317 NES 230317 2023 MAR 17 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Investigators discuss new findings in pharmaceuticals. [Extracted from the article]
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- 2023
166. University of Bologna Researchers Update Knowledge of Regenerative Medicine (Cytochalasin B Influences Cytoskeletal Organization and Osteogenic Potential of Human Wharton's Jelly Mesenchymal Stem Cells).
- Abstract
Keywords: Bioengineering; Biological Factors; Biomedical Engineering; Biomedicine; Biotechnology; Cytochalasins; Health and Medicine; Mesenchymal Stem Cells; Mycotoxins; Regenerative Medicine; Stem Cell Research EN Bioengineering Biological Factors Biomedical Engineering Biomedicine Biotechnology Cytochalasins Health and Medicine Mesenchymal Stem Cells Mycotoxins Regenerative Medicine Stem Cell Research 523 523 1 03/23/23 20230316 NES 230316 2023 MAR 16 (NewsRx) -- By a News Reporter-Staff News Editor at Stem Cell Week -- Researchers detail new data in regenerative medicine. Keywords for this news article include: University of Bologna, Bologna, Italy, Europe, Biotechnology, Biomedical Engineering, Biomedicine, Mycotoxins, Cytochalasins, Bioengineering, Biological Factors, Stem Cell Research, Health and Medicine, Regenerative Medicine, Mesenchymal Stem Cells. Bioengineering, Biological Factors, Biomedical Engineering, Biomedicine, Biotechnology, Cytochalasins, Health and Medicine, Mesenchymal Stem Cells, Mycotoxins, Regenerative Medicine, Stem Cell Research. [Extracted from the article]
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- 2023
167. Study Findings on Breast Cancer Described by Researchers at Kazan Federal University (Cytochalasin B-Induced Membrane Vesicles from TRAIL-Overexpressing Mesenchymal Stem Cells Induce Extrinsic Pathway of Apoptosis in Breast Cancer Mouse Model).
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For more information on this research see: Cytochalasin B-Induced Membrane Vesicles from TRAIL-Overexpressing Mesenchymal Stem Cells Induce Extrinsic Pathway of Apoptosis in Breast Cancer Mouse Model. Keywords: Apoptosis; Biological Factors; Breast Cancer; Cancer; Cellular Physiology; Cytochalasins; Drugs and Therapies; Genetics; Health and Medicine; Mesenchymal Stem Cells; Mycotoxins; Oncology; Stem Cell Research; Women's Health EN Apoptosis Biological Factors Breast Cancer Cancer Cellular Physiology Cytochalasins Drugs and Therapies Genetics Health and Medicine Mesenchymal Stem Cells Mycotoxins Oncology Stem Cell Research Women's Health 2023 FEB 7 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Investigators discuss new findings in breast cancer. [Extracted from the article]
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- 2023
168. Cytochalasins and an Abietane-Type Diterpenoid with Allelopathic Activities from the Endophytic Fungus Xylaria Species
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Gennaro Pescitelli, Jian Xiao, Jin-Ming Gao, Hui-Yi Zhou, Yi-Jie Zhai, Wen-Bo Han, and Yu-Qi Gao
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0106 biological sciences ,Cytochalasin E ,Toona sinensis ,diterpenoid ,Xylaria ,phytotoxicity ,01 natural sciences ,chemistry.chemical_compound ,herbicides ,Botany ,Endophytes ,Xylaria sp ,Cytochalasin ,Meliaceae ,Triticum ,Allelopathy ,allelopathic activities ,cytochalasins ,endophyte ,Brassica napus ,Cytochalasins ,Diterpenes, Abietane ,Molecular Structure ,Xylariales ,Abietane ,biology ,010401 analytical chemistry ,food and beverages ,General Chemistry ,biology.organism_classification ,0104 chemical sciences ,chemistry ,Abietanes ,Shoot ,Phytotoxicity ,Diterpenes ,General Agricultural and Biological Sciences ,010606 plant biology & botany - Abstract
Bioactivity-guided isolation of the cultures of the endophytic fugus Xylaria sp. XC-16 residing in a deciduous tree Toona sinensis led to the discovery of four new allelochemicals (1-4), including three cytochalasins, epoxycytochalasin Z17 (1), epoxycytochalasin Z8 (2), and epoxyrosellichalasin (3), and an abietane-type diterpenoid, hydroxyldecandrin G (4), along with four known analogues, 10-phenyl-[12]-cytochalasins Z16 (5) and Z17 (6), cytochalasin K (7), and cytochalasin E (8). The structures of these compounds were elucidated by comprehensive spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism (CD) and X-ray diffraction. All of the chemicals were tested for their allelopathic effects on turnip ( Raphanus sativus) and wheat ( Triticum aestivum). Notably, compounds 3, 4, and 7 strongly inhibited wheat shoot elongation, and compounds 5, 7, and 8 inhibited wheat root elongation, showing comparable IC50 values to the positive control glyphosate. Meanwhile, compound 8 was a potential inhibitor on turnip root elongation, with an IC50 value of 1.57 ± 0.21 μM, which was 50-fold more potent than glyphosate. Nevertheless, compounds 5 and 7 stimulated turnip shoot elongation at lower concentrations.
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- 2019
169. [11]-chaetoglobosins with cytotoxic activities from Pseudeurotium bakeri.
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Duan, Fangfang, Gao, Ying, Peng, Xiaogang, Meng, Xianggao, Chang, Jinling, Gan, Yutian, Ouyang, Qianxi, and Ruan, Hanli
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APOPTOSIS , *CELL cycle , *CYTOCHALASINS , *CANCER cells , *CELL lines , *ENDOPHYTIC fungi - Abstract
[Display omitted] • Fourteen new [11]-chaetoglobosins (1 – 14) were characterized from Pseudeurotium bakeri P 1-1-1. • 1 showed significant cytotoxic effects against seven human cancer cell lines with IC 50 values of 5.1 ± 0.9–10.8 ± 0.1 μM. • 1 dose-dependently induced G2/M cell cycle arrest and apoptosis in MCF-7, HeLa, and HCT116 cells. • The mechanism involved in the G2/M cell cycle arrest and apoptosis of 1 in MCF-7 cells was associated with downregulating of cyclin B1 and Cdk1, and activating of Bcl-2/caspase-3/PARP pathway. Fourteen new [11]-chaetoglobosins (1 – 14), along with two known congeners, cytochalasins X and Y (15 and 16), were isolated from the cultures of an endophytic fungus Pseudeurotium bakeri P 1-1-1. Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of one- and two-dimensional NMR data, HRESIMS spectrometry, chemical methods, and single-crystal X-ray diffraction analysis (Cu Kα). All isolates were evaluated for their cytotoxic activities and chaetopseudeurin M (1) displayed significant cytotoxic effects against seven human cancer cell lines, with IC 50 values ranging from 5.1 ± 0.9 to 10.8 ± 0.1 μM. Western blot experiments exhibited that compound 1 exerted its cytotoxic effect in MCF-7 cells by inducing G2/M cell cycle arrest and apoptosis via downregulating the expression of cyclin B1 and Cdk1, and activating Bcl-2/caspase-3/PARP pathway, respectively. [ABSTRACT FROM AUTHOR]
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- 2022
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170. Participation of actin filaments, myosin and phosphatidylinositol 3-kinase in the formation and polarisation of tetraspore germ tube of Gelidium floridanum (Rhodophyta, Florideophyceae )
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Debora T. Pereira, Zenilda L. Bouzon, Carmen Simioni, Elisa Poltronieri Filipin, and Luciane Cristina Ouriques
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0106 biological sciences ,Chloroplasts ,Morpholines ,Germ tube ,Diacetyl ,macromolecular substances ,Plant Science ,Myosins ,Biology ,010603 evolutionary biology ,01 natural sciences ,Cell wall ,chemistry.chemical_compound ,Cell Wall ,Myosin ,Phosphatidylinositol ,Cytoskeleton ,Cytochalasin B ,Ecology, Evolution, Behavior and Systematics ,Actin ,Phosphoinositide-3 Kinase Inhibitors ,General Medicine ,Bridged Bicyclo Compounds, Heterocyclic ,Cytochalasins ,Actin Cytoskeleton ,chemistry ,Chromones ,Cytoplasm ,Rhodophyta ,Biophysics ,Thiazolidines ,Phosphatidylinositol 3-Kinase ,Plant Structures ,010606 plant biology & botany - Abstract
This study aimed to examine the evidence of direct interaction among actin, myosin and phosphatidylinositol 3-kinase (PI3K) in the polarisation and formation of the tetraspore germ tube of Gelidium floridanum. After release, tetraspores were exposed to cytochalasin B, latrunculin B, LY294002 and BDM for a period of 6 h. In control samples, formation of the germ tube occurred after the experimental period, with cellulose formation and elongated chloroplasts moving through the tube region in the presence of F-actin. In the presence of cytochalasin B, an inhibitor of F-actin, latrunculin B, an inhibitor of G-actin, and BDM, a myosin inhibitor, tetraspores showed no formation of the germ tube or cellulose. Spherical-shaped chloroplasts were observed in the central region with a few F-actin filaments in the periphery of the cytoplasm. Tetraspores treated with LY294002, a PI3K inhibitor, showed no formation of the tube at the highest concentrations. Polarisation of cytoplasmic contents did not occur, only cellulose formation. It was concluded that F-actin directs the cell wall components and contributes to the maintenance of chloroplast shape and elongation during germ tube formation. PI3K plays a fundamental role in signalling for the asymmetric polarisation of F-actin. Thus, F-actin regulates the polarisation and germination processes of tetraspores of G. floridanum.
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- 2018
171. Diagnostic fragmentation filtering for the discovery of new chaetoglobosins and cytochalasins
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Cobus M. Visagie, David R. McMullin, Jacob P. Walsh, Ashraf S. Ibrahim, Joey B. Tanney, Justin B. Renaud, Mark W. Sumarah, Shawn Hoogstra, and Ken K.-C. Yeung
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Stereochemistry ,Electrospray ionization ,Drug Evaluation, Preclinical ,Chaetomium ,Mass spectrometry ,Tandem mass spectrometry ,01 natural sciences ,Indole Alkaloids ,Analytical Chemistry ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,Drug Discovery ,Metabolomics ,Cytochalasin ,Spectroscopy ,Cytochalasin D ,Natural product ,Xylariales ,biology ,Chaetomium globosum ,010401 analytical chemistry ,Organic Chemistry ,Penicillium ,biology.organism_classification ,Cytochalasins ,0104 chemical sciences ,chemistry ,Fermentation ,Software ,Chromatography, Liquid - Abstract
Rationale Microbial natural products are often biosynthesized as classes of structurally related compounds that have similar tandem mass spectrometry (MS/MS) fragmentation patterns. Mining MS/MS datasets for precursor ions that share diagnostic or common features enables entire chemical classes to be identified, including novel derivatives that have previously been unreported. Analytical data analysis tools that can facilitate a class-targeted approach to rapidly dereplicate known compounds and identify structural variants within complex matrices would be useful for the discovery of new natural products. Methods A diagnostic fragmentation filtering (DFF) module was developed for MZmine to enable the efficient screening of MS/MS datasets for class-specific product ions(s) and/or neutral loss(es). This approach was applied to series of the structurally related chaetoglobosin and cytochalasin classes of compounds. These were identified from the culture filtrates of three fungal genera: Chaetomium globosum, a putative new species of Penicillium (called here P. cf. discolor: closely related to P. discolor), and Xylaria sp. Extracts were subjected to LC/MS/MS analysis under positive electrospray ionization and operating in a data-dependent acquisition mode, performed using a Thermo Q-Exactive mass spectrometer. All MS/MS datasets were processed using the DFF module and screened for diagnostic product ions at m/z 130.0648 and 185.0704 for chaetoglobosins, and m/z 120.0808 and 146.0598 for cytochalasins. Results Extracts of C. globosum and P. cf. discolor strains revealed different mixtures of chaetoglobosins, whereas the Xylaria sp. produced only cytochalasins; none of the strains studied produced both classes of compounds. The dominant chaetoglobosins produced by both C. globosum and P. cf. discolor were chaetoglobosins A, C, and F. Tetrahydrochaetoglobosin A was identified from P. cf. discolor extracts and is reported here for the first time as a natural product. The major cytochalasins produced by the Xylaria sp. were cytochalasin D and epoxy cytochalasin D. A larger unknown "cytochalasin-like" molecule with the molecular formula C38 H47 NO10 was detected from Xylaria sp. culture filtrate extracts and is a current target for isolation and structural characterization. Conclusions DFF is an effective LC/MS data analysis approach for rapidly identifying entire classes of compounds from complex mixtures. DFF has proved useful in the identification of new natural products and allowing for their partial characterization without the need for isolation.
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- 2018
172. Armochaetoglasins A–I: Cytochalasan alkaloids from fermentation broth of Chaetomium globosum TW1-1 by feeding L-tyrosine
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Jianping Wang, Yonghui Zhang, Chunmei Chen, Weixi Gao, Weiguang Sun, Zhengxi Hu, Hucheng Zhu, Yongbo Xue, Yan He, Chenwei Chai, and Fengli Li
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Circular dichroism ,Stereochemistry ,Molecular Conformation ,Plant Science ,Fungus ,Chaetomium ,Horticulture ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Alkaloids ,Chaetomiaceae ,Tyrosine ,Molecular Biology ,biology ,Chaetomium globosum ,010405 organic chemistry ,Chemistry ,Alkaloid ,General Medicine ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,Cytochalasins ,0104 chemical sciences ,Fermentation ,Antibacterial activity - Abstract
By feeding L-tyrosine into the culture medium, nine undescribed compounds, termed as armochaetoglasins A–I, together with three known analogues, namely armochaetoglobin E, chaetoglobosin V, and chaetoglobosin J, were isolated and identified from the medicinal terrestrial arthropod-derived fungus Chaetomium globosum TW1-1. Their structures were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of their electronic circular dichroism (ECD) spectra. Structurally, armochaetoglasin A represented the first tyrosine-derived cytochalasan alkaloid characterized by a 13-membered carbocyclic ring system; armochaetoglasins B and C possessed a rare 19,20-seco-chaetoglobosin skeleton. Armochaetoglasin B, chaetoglobosin V, and chaetoglobosin J showed weak cytotoxic activity with IC50 values ranging from 19.5 to 34.72 μM.
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- 2018
173. Bisaspochalasins D and E: Two Heterocycle-Fused Cytochalasan Homodimers from an Endophytic
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Li, Wang, Zhiyin, Yu, Xiaowei, Guo, Jian-Ping, Huang, Yijun, Yan, Sheng-Xiong, Huang, and Jing, Yang
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Aspergillus ,Molecular Structure ,Humans ,HL-60 Cells ,Cytochalasins - Abstract
Two heterocycle-fused cytochalasan homodimers, bisaspochalasins D (
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- 2021
174. Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis
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Nipatthra Phromma-in, Pichayada Somboon, Nitnipa Soontorngun, Kwanrutai Watchaputi, and Khanok Ratanakhanokchai
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0301 basic medicine ,Cell biology ,Antifungal Agents ,Molecular biology ,Science ,030106 microbiology ,Saccharomyces cerevisiae ,Cell ,Mutant ,Biochemistry ,Microbiology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Lipid droplet ,Genetics ,medicine ,Cytoskeleton ,Actin ,Ergosterol ,Multidisciplinary ,Xylariales ,biology ,Drug discovery ,Methyltransferases ,Lipid Metabolism ,biology.organism_classification ,Chemical biology ,Cytochalasins ,Actins ,Yeast ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Medicine ,Biotechnology - Abstract
Repetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ’s transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.
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- 2021
175. Progress in the Chemistry of Cytochalasans
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Hucheng, Zhu, Chunmei, Chen, Qingyi, Tong, Yuan, Zhou, Ying, Ye, Lianghu, Gu, and Yonghui, Zhang
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Biological Products ,Fungi ,Cytochalasins ,Dimerization - Abstract
Cytochalasans are a group of fungal-derived natural products characterized by a perhydro-isoindolone core fused with a macrocyclic ring, and they exhibit a high structural diversity and a broad spectrum of bioactivities. Cytochalasans have attracted significant attention from the chemical and pharmacological communities and have been reviewed previously from various perspectives in recent years. However, continued interest in the cytochalasans and the number of laboratory investigations on these compounds are both growing rapidly. This contribution provides a general overview of the isolation, structural determination, biological activities, biosynthesis, and total synthesis of cytochalasans. In total, 477 cytochalasans are covered, including "merocytochalasans" that arise by the dimerization or polymerization of one or more cytochalasan molecules with one or more other natural product units. This contribution provides a comprehensive treatment of the cytochalasans, and it is hoped that it may stimulate further work on these interesting natural products.
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- 2021
176. Hypermutator Salmonella Heidelberg induces an early cell death in epithelial cells.
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Le Gall-David, Sandrine, Zenbaa, Neila, Bouchard, Damien, Lavault, Marie-Thérèse, Bonnaure-Mallet, Martine, Jolivet-Gougeon, Anne, and Bousarghin, Latifa
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SALMONELLA diseases , *CELL death , *EPITHELIAL cells , *CYTOSKELETON formation , *CYTOCHALASINS - Abstract
We have previously described that a strain of Salmonella Heidelberg with a hypermutator phenotype, B182, adhered strongly to HeLa cells. In this work, we showed that this hypermutator Salmonella strain invaded HeLa epithelial cells and induced cytoskeleton alteration. Those changes lead to HeLa cell death which was characteristic of apoptosis. For the first time, we showed that this hypermutator strain induced apoptosis associated with the activation of caspases 2, 9 and 3. Complementation of B182 strain showed a decrease in cells death induction. In the presence of other Salmonella Heidelberg with a normomutator phenotype, such as WT and SL486, cell death and caspase 3 were undetectable. These results suggested that early apoptosis and caspase 3 activation were specific to B182. Besides, B182 induced LDH release and caspase 3 activation in CaCo-2 and HCT116 cells. Heat-treated B182 and diffusible products failed to induce this phenotype. Epithelial cells treatment with cytochalasin D caused the inhibition of B182 internalisation and caspase 3 activation. These results showed that this cell death required active S . Heidelberg B182 protein synthesis and bacterial internalisation. However sipB and sopB , usually involved in apoptosis induced by Salmonella were not overexpressed in B182, contrary to fimA and fliC . Comparative genome analysis showed numerous mutations as in rpoS which would be more investigated. The role of the hypermutator phenotype might be suspected to be implicated in these specific features. This result expands our knowledge about strong mutators frequently found in bacterial organisms isolated from clinical specimens. [ABSTRACT FROM AUTHOR]
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- 2015
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177. Sesquiterpenes and other constituents of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp.
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Wei, Han, Xu, Ya-ming, Espinosa-Artiles, Patricia, Liu, Manping X., Luo, Jiang-Guang, U’Ren, Jana M., Elizabeth Arnold, A., and Leslie Gunatilaka, A.A.
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XYLARIA , *CELL lines , *CYTOCHALASINS , *ENDOPHYTIC fungi , *NUCLEAR magnetic resonance spectroscopy , *CELL-mediated cytotoxicity - Abstract
Oxygenated guaiane-type sesquiterpenes, xylaguaianols A−D ( 1 – 4 ), an iso-cadinane-type sesquiterpene isocadinanol A ( 5 ), and an α -pyrone 9-hydroxyxylarone ( 6 ), together with five known sesquiterpenes ( 7 – 11 ), and four known cytochalasins ( 12 – 15 ) were isolated from a culture broth of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp. The structures of all compounds were elucidated by the analysis of their spectroscopic data and relative configurations of 1 – 5 were determined with the help of NMR NOESY experiments. Cytochalasins C ( 12 ), D ( 13 ), and Q ( 14 ) were investigated for their cytotoxic activity against five tumor cell lines. Cytochalasin D showed significant cytotoxicity against all five cell lines, with IC 50 s ranging from 0.22 to 1.44 μM, whereas cytochalasins C and Q exhibited moderate, but selective cytotoxicity. [ABSTRACT FROM AUTHOR]
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- 2015
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178. The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis.
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Jayaprakash, K., Demirel, I., Khalaf, H., and Bengtsson, T.
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PORPHYROMONAS gingivalis infections , *PHAGOCYTOSIS , *OXIDATIVE stress , *NEUTROPHILS , *CYTOCHALASINS , *PERIODONTAL disease - Abstract
Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps ( NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria. [ABSTRACT FROM AUTHOR]
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- 2015
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179. Endocytosed 2-Microglobulin Amyloid Fibrils Induce Necrosis and Apoptosis of Rabbit Synovial Fibroblasts by Disrupting Endosomal/Lysosomal Membranes: A Novel Mechanism on the Cytotoxicity of Amyloid Fibrils.
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Okoshi, Tadakazu, Yamaguchi, Itaru, Ozawa, Daisaku, Hasegawa, Kazuhiro, and Naiki, Hironobu
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AMYLOIDOSIS diagnosis , *HEMODIALYSIS , *MICROGLOBULINS , *CYTOCHALASINS , *APOPTOSIS - Abstract
Dialysis-related amyloidosis is a major complication in long-term hemodialysis patients. In dialysis-related amyloidosis, β2-microglobulin (β2-m) amyloid fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome and destructive arthropathy with cystic bone lesions, but the mechanism by which these amyloid fibrils destruct bone and joint tissue is not fully understood. In this study, we assessed the cytotoxic effect of β2-m amyloid fibrils on the cultured rabbit synovial fibroblasts. Under light microscopy, the cells treated with amyloid fibrils exhibited both necrotic and apoptotic changes, while the cells treated with β2-m monomers and vehicle buffer exhibited no morphological changes. As compared to β2-m monomers and vehicle buffer, β2-m amyloid fibrils significantly reduced cellular viability as measured by the lactate dehydrogenase release assay and the 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay and significantly increased the percentage of apoptotic cells as measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. β2-m amyloid fibrils added to the medium adhered to cell surfaces, but did not disrupt artificial plasma membranes as measured by the liposome dye release assay. Interestingly, when the cells were incubated with amyloid fibrils for several hours, many endosomes/lysosomes filled with amyloid fibrils were observed under confocal laser microscopy and electron microscopy, Moreover, some endosomal/lysosomal membranes were disrupted by intravesicular fibrils, leading to the leakage of the fibrils into the cytosol and adjacent to mitochondria. Inhibition of actin-dependent endocytosis by cytochalasin D attenuated the toxicity of amyloid fibrils. These results suggest that endocytosed β2-m amyloid fibrils induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes, and this novel mechanism on the cytotoxicity of amyloid fibrils is described. [ABSTRACT FROM AUTHOR]
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- 2015
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180. Effects of cytochalasin congeners, microtubule-directed agents, and doxorubicin alone or in combination against human ovarian carcinoma cell lines in vitro.
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Trendowski, Matthew, Christen, Timothy D., Acquafondata, Christopher, and Fondy, Thomas P.
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OVARIAN cancer treatment , *CYTOCHALASINS , *MICROTUBULES , *DOXORUBICIN , *COMBINATION drug therapy , *CELL lines , *CANCER chemotherapy , *ANTINEOPLASTIC agents , *ANTINEOPLASTIC antibiotics , *CYTOPLASM , *DRUG resistance , *DRUG design , *CLINICAL drug trials , *OVARIAN tumors , *INDOLE compounds , *PHARMACODYNAMICS ,OVARIAN cancer patients - Abstract
Background: Although the actin cytoskeleton is vital for carcinogenesis and subsequent pathology, no microfilament-directed agent has been approved for cancer chemotherapy. One of the most studied classes of microfilament-directed agents has been the cytochalasins, mycotoxins known to disrupt the formation of actin polymers. In the present study, we sought to determine the effects of cytochalasin congeners toward human drug sensitive and multidrug resistant cell lines.Methods: SKOV3 human ovarian carcinoma and several multidrug resistant derivatives were tested for sensitivity against a panel of nine cytochalasin congeners, as well as three clinically approved chemotherapeutic agents (doxorubicin, paclitaxel, and vinblastine). In addition, verapamil, a calcium ion channel blocker known to reverse P-glycoprotein (P-gp) mediated drug resistance, was used in combination with multiple cytochalasin congeners to determine whether drug sensitivity could be increased.Results: While multidrug resistant SKVLB1 had increased drug tolerance (was more resistant) to most cytochalasin congeners in comparison to drug sensitive SKOV3, the level of resistance was 10 to 1000-fold less for the cytochalasins than for any of the clinically approved agents. While cytochalasins did not appear to alter the expression of ATP binding cassette (ABC) transporters, several cytochalasins appeared to inhibit the activity of ABC transporter-mediated efflux of rhodamine 123 (Rh123), suggesting that these congeners do have affinity for drug efflux pumps. Cytochalasins also appeared to significantly decrease the F/G-actin ratio in both drug sensitive and drug resistant cells, indicative of marked microfilament inhibition. The cytotoxicity of most cytochalasin congeners could be increased with the addition of verapamil, and the drug sensitivity of resistant SKVLB1 to the clinically approved antineoplastic agents could be increased with the addition of cytochalasins. As assessed by isobolographic analysis and Chou-Talalay statistics, cytochalasin B and 21,22-dihydrocytochalasin B (DiHCB) demonstrated notable synergy with doxorubicin and paclitaxel, warranting further investigation in a tumor-bearing mammalian model.Conclusion: Cytochalasins appear to inhibit the activity of P-gp and potentially other ABC transporters, and may have novel activity against multidrug resistant neoplastic cells that overexpress drug efflux proteins. [ABSTRACT FROM AUTHOR]- Published
- 2015
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181. Intracellular dehydroascorbic acid inhibits SVCT2-dependent transport of ascorbic acid in mitochondria.
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Fiorani, Mara, Azzolini, Catia, Guidarelli, Andrea, Cerioni, Liana, Scotti, Maddalena, and Cantoni, Orazio
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VITAMIN C , *SODIUM cotransport systems , *MITOCHONDRIAL physiology , *DITHIOTHREITOL , *CYTOCHALASINS , *SULFINPYRAZONE - Abstract
Exposure of U937 cells to low concentrations of l -ascorbic acid (AA) is associated with a prompt cellular uptake and a further mitochondrial accumulation of the vitamin. Under the same conditions, dehydroascorbic acid (DHA) uptake was followed by rapid reduction and accumulation of identical intracellular levels of AA, however, in the absence of significant mitochondrial uptake. This event was instead observed after exposure to remarkably greater concentrations of DHA. Furthermore, experiments performed in isolated mitochondria revealed that DHA transport through hexose transporters and Na + -dependent transport of AA were very similar. These results suggest that the different subcellular compartmentalization of the vitamin is mediated by events promoting inhibition of mitochondrial AA transport, possibly triggered by low levels of DHA. We obtained results in line with this notion in intact cells, and more direct evidence in isolated mitochondria. This inhibitory effect was promptly reversible after DHA removal and comparable with that mediated by established inhibitors, as quercetin. The results presented collectively indicate that low intracellular concentrations of DHA, because of its rapid reduction back to AA, are a poor substrate for direct mitochondrial uptake. DHA concentrations, however, appear sufficiently high to mediate inhibition of mitochondrial transport of AA/DHA-derived AA. [ABSTRACT FROM AUTHOR]
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- 2015
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182. Cytotoxic cytochalasins from the endophytic fungus Eutypella scoparia PSU-H267.
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Kongprapan, Thippaya, Rukachaisirikul, Vatcharin, Saithong, Saowanit, Phongpaichit, Souwalak, Poonsuwan, Wimarak, and Sakayaroj, Jariya
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Eleven compounds including one new cytochalasin derivative, scoparasin C ( 1 ), four cytochalasins ( 2 – 5 ), four pimarane diterpenes ( 6 – 9 ) and two chromene derivatives ( 10 and 11 ) were obtained from a culture broth of Eutypella scoparia PSU-H267 which was isolated from a leaf of Hevea brasiliensis . Their structures were determined by spectroscopic evidence. For compounds 2 , 3 and 5 , the structures were confirmed by single-crystal X-ray diffraction crystallography. Compounds 1 , 3 , 4 and 7 were strongly active against Vero cell lines with IC 50 values of 1.19, 0.04, 1.01 and 2.50 μM, respectively. Only compound 3 displayed potent cytotoxic activity towards KB-oral cavity cancer cell lines with the IC 50 value of 2.46 μM. [ABSTRACT FROM AUTHOR]
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- 2015
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183. Morphological change of CD4+ T cell during contact with DC modulates T-cell activation by accumulation of F-actin in the immunology synapse.
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Wei Lin, Yuanzhen Suo, Yuting Deng, Zhichao Fan, Yijie Zheng, Xunbin Wei, and Yiwei Chu
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T cells , *F-actin , *SYNAPSES , *PROTEIN kinases , *CYTOCHALASINS - Abstract
Background: The changes in T-cell morphology during immunological synapse (IS) formation are essential for T-cell activation. Previous researches have shown that T cell changed from spherical to elongated and/or flattened during in contact with B cell. As most powerful antigen presenting cell, dendritic cell (DC) has a strong ability to activate T cells. However, the morphological change of T cell which contacts DC and the relationship between morphological change and T-cell activation are not very clear. Thus, we studied the morphological change of CD4+ T cell during contact with DC. Results: Using live-cell imaging, we discovered diversity in the T-cell morphological changes during contact with DCs. The elongation-flattening of CD4+ T cells correlated with a low-level Ca2+ response and a loss of T-cell receptor (TCR) signalling molecules in the IS, including zeta-chain associated protein kinase 70 (ZAP-70), phospholipase C-γ (PLC-γ) and protein kinase C-ϑ (PKC-ϑ), whereas rounding-flattening correlated with sufficient CD4+ T-cell activation. Different morphological changes were correlated with the different amount of accumulated filamentous actin (F-actin) in the IS. Disruption of F-actin by cytochalasin D impaired the morphological change and the localisation of calcium microdomains in the IS and decreased the calcium response in CD4+ T cells. Conclusion: Our study discovered the diversity in morphological change of T cells during contacted with DCs. During this process, the different morphological changes of T cells modulate T-cell activation by the different amount of F-actin accumulation in the IS, which controls the distribution of calcium microdomains to affect T-cell activation. [ABSTRACT FROM AUTHOR]
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- 2015
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184. Cystic fibrosis transmembrane conductance regulator is involved in polyphenol-induced swelling of the endothelial glycocalyx.
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Peters, Wladimir, Kusche-Vihrog, Kristina, Oberleithner, Hans, and Schillers, Hermann
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CYSTIC fibrosis transmembrane conductance regulator ,POLYPHENOLS ,GLYCOCALYX ,HOMEOSTASIS ,CYTOCHALASINS ,ENDOTHELIUM diseases ,NANOINDENTATION - Abstract
Previous studies show that polyphenol-rich compounds can induce a swelling of the endothelial glycocalyx (eGC). Our goal was to reveal the mechanism behind the eGC-swelling. As polyphenols are potent modulators of fibrosis transmembrane conductance regulator (CFTR) Cl − channel, the hypothesis was tested whether polyphenol-induced increase in CFTR activity is responsible for the eGC-swelling. The impact of the polyphenols resveratrol, (−)-epicatechin, and quercetin on nanomechanics of living endothelial GM7373 cells was monitored by AFM-nanoindentation. The tested polyphenols lead to eGC-swelling with a simultaneous decrease in cortical stiffness. EGC-swelling, but not the change in cortical stiffness, was prevented by the inhibition of CFTR. Polyphenol-induced eGC-swelling could be mimicked by cytochalasin D, an actin-depolymerizing agent. Thus, in the vascular endothelium, polyphenols induce eGC-swelling by softening cortical actin and activating CFTR. Our findings imply that CFTR plays an important role in the maintenance of vascular homeostasis and may explain the vasoprotective properties of polyphenols. From the Clinical Editor Many vascular problems clinically can be attributed to a dysregulation of endothelial glycocalyx (eGC). The underlying mechanism however remains unclear. In this article, the authors used nanoindentation and showed that polyphenols could swell the endothelial glycocalyx and alter its function. This investigative method can lead to further mechanistic studies of other molecular pathways. [ABSTRACT FROM AUTHOR]
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- 2015
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185. Rho-kinase-dependent actin turnover and actomyosin disassembly are necessary for mouse spinal neural tube closure.
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Escuin, Sarah, Vernay, Bertrand, Savery, Dawn, Gurniak, Christine B., Witke, Walter, Greene, Nicholas D. E., and Copp, Andrew J.
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RHO-associated kinases , *ACTIN , *ACTOMYOSIN , *SPINAL nerves , *CYTOCHALASINS , *LABORATORY mice - Abstract
The cytoskeleton is widely considered essential for neurulation, yet the mouse spinal neural tube can close despite genetic and non-genetic disruption of the cytoskeleton. To investigate this apparent contradiction, we applied cytoskeletal inhibitors to mouse embryos in culture. Preventing actomyosin cross-linking, F-actin assembly or myosin II contractile activity did not disrupt spinal closure. In contrast, inhibiting Rho kinase (ROCK, for which there are two isoforms ROCK1 and ROCK2) or blocking F-actin disassembly prevented closure, with apical F-actin accumulation and adherens junction disturbance in the neuroepithelium. Cofilin-1-null embryos yielded a similar phenotype, supporting the hypothesis that there is a key role for actin turnover. Co-exposure to Blebbistatin rescued the neurulation defects caused by RhoA inhibition, whereas an inhibitor of myosin light chain kinase, ML-7, had no such effect. We conclude that regulation of RhoA, Rho kinase, LIM kinase and cofilin signalling is necessary for spinal neural tube closure through precise control of neuroepithelial actin turnover and actomyosin disassembly. In contrast, actomyosin assembly and myosin ATPase activity are not limiting for closure. [ABSTRACT FROM AUTHOR]
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- 2015
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186. Chemically assisted somatic cell nuclear transfer without micromanipulator in the goat: effects of demecolcine, cytochalasin-B, and MG-132 on the efficiency of a manual method of oocyte enucleation using a pulled Pasteur pipette.
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Hosseini, S.M., Hajian, M., Forouzanfar, M., Ostadhosseini, S., Moulavi, F., Ghanaei, H.R., Gourbai, H., Shahverdi, A.H., Vosough, A.D., and Nasr-Esfahani, M.H.
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SOMATIC cell nuclear transfer , *MICROMANIPULATORS , *CYTOCHALASINS , *OVUM , *CELL enucleation - Abstract
The present study aimed to facilitate widespread application of a previously described manual method of somatic cell nuclear transfer (SCNT) by investigating the effects of demecolcine (a microtubule-depolymerizing chemical), cytochalasin-B (a microfilament-depolymerizing chemical: 2.5 μg/ml for 15 min) and MG-132 (a proteasome inhibitor chemical) on the (i) incidence of cytoplasmic protrusion of MII chromosomes, (ii) improvement of manual oocyte enucleation, and (iii) in vitro and in vivo developmental competence of SCNT embryos in the goat. Following in vitro maturation, around 65% of goat oocytes contained a characteristic cytoplasmic protrusion of MII-chromosomes. Treatment with demecolcine (0.4 μg/ml for 30 min) significantly increased this rate to 92.2 ± 4.5%. Treatment with MG-132 (2 μM for 30 min) could not improve this rate when used alone (61.4 ± 11.5%), but when combined with demecolcine (86.4 ± 8.1%). Treatment with cytochalasin-B completely suppressed this rate whenever used, either alone (7.7 ± 5.1%) or in combination with demecolcine (3.9 ± 1.3%). In a direct comparison, there was no significant difference in quantity and quality of embryos propagated by the manual vs. micromanipulation-based methods of SCNT (cleavage: 85.3 ± 4.5 vs. 89.5 ± 8.9%, blastocyst: 19.5 ± 4.3 vs. 24.3 ± 4.4%, grade 1 and 2 blastocyst: 33.8 ± 7.1 vs. 29.5 ± 6.3%, total cell count: 125 ± 11.1 vs. 122 ± 10.5, respectively). Furthermore, development to live kids at term was not significant between the two SCNT methods. From both technical and economical points of view, the overall in vitro and in vivo efficiency of this manual method of SCNT proved it a simple, fast and efficient alternative for large scale production of cloned goats. [ABSTRACT FROM AUTHOR]
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- 2015
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187. Cryopreservation of in vitro–produced sheep embryos: Effects of different protocols of lipid reduction.
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Romão, R., Marques, C.C., Baptista, M.C., Barbas, J.P., Horta, A.E.M., Carolino, N., Bettencourt, E., and Pereira, R.M.
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CRYOPRESERVATION of organs, tissues, etc. , *SHEEP embryos , *ISOPRENYLATION , *CONJUGATED linoleic acid , *CYTOCHALASINS , *IN vitro studies - Abstract
The low survival of sheep in vitro –produced (IVP) embryos after cryopreservation is a key limiting step to the widespread of this technology. In the present work, different approaches for enhancing cryosurvival of these embryos were compared: embryo delipidation by centrifugation in the absence or presence of cytochalasin D, a cytoskeleton stabilizer or by embryo culture in the presence of different doses of the trans -10 cis -12–conjugated linoleic acid isomer (CLA). Three experiments were conducted. In experiment 1, IVP blastocysts before vitrification were randomly distributed into four groups: control; centrifuged (cent), cytochalasin D (cyto-D), centrifuged + cytochalasin D (cent + cyto-D). In experiment 2, different doses of CLA (25, 50, and 100 μM) were supplemented during embryo culture before vitrification of blastocysts. A control group ran simultaneously. A third experiment was performed to compare both approaches from the previous ones but without the groups with the worst results (groups: control, cyto-D, cent + cyto-D, CLA25, CLA50). In all experiments, embryos integrity and reexpansion were assessed after warming and after 3 hours of culture. In experiment 1, the postwarming integrity rate was the lowest (P < 0.05) in embryos from the cent group (cent: 50.6 ± 10.3% vs. control: 74.6 ± 9.2%, cyto-D: 92.3 ± 9.7%, and cent + cyto-D: 90.5 ± 11.2%), whereas the best (P < 0.05) reexpansion scores were obtained in cent + cyto-D embryos (cent + cyto-D: 2.6 ± 0.28 vs. control: 1.8 ± 0.08, cent: 1.9 ± 0.2, and cyto-D: 1.8 ± 0.31). In experiments 2 and 3, higher (P < 0.05) cleavage rates were observed in CLA25 (50.9 ± 6.2% and 49.2 ± 5.6%, respectively) and CLA50 (48.9 ± 6.2% and 47.6 ± 5.6%, respectively) than those in the control (41.8 ± 6.1% and 40.4 ± 5.4%, respectively) group. In experiment 2, CLA100 presented the lowest (P < 0.002) Day-6 and -7 embryo production rate and quality. After warming, superior (P < 0.02) expansion scores were achieved in CLA25 (3.1 ± 0.29) and CLA50 (3.8 ± 0.17) than in the control (1.9 ± 0.10) group. Similar results were attained in experiment 3. However, although cent + cyto-D embryos showed higher (P = 0.008) postwarming expansion scores than the control (2.8 ± 0.29 vs. 1.9 ± 0.07) group, this score was lower (P = 0.0009) than that in CLA50 embryos (3.8 ± 0.17). In conclusion, our results showed that different protocols of lipid reduction can be successfully applied to improve the cryotolerance of IVP sheep embryos. [ABSTRACT FROM AUTHOR]
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- 2015
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188. Analysis of Chaetoconvosins a and B Using Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry.
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Xu, Guo-Bo, Fang, Dong-Mei, Li, Guo-You, Zhang, Guo-Lin, and Wu, Zhi-Jun
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CYTOCHALASINS , *ELECTROSPRAY ionization mass spectrometry , *CHEMICAL reactions , *PLANT chemical analysis , *BOTANICAL chemistry - Abstract
Two novel cytochalasins, chaetoconvosins A and B, isolated from Chaetomium convolutum were investigated using electrospray quadrupole time-of-flight tandem mass spectrometry (ESI-QTOF-MS/MS) in positive-ion mode. The main product ions in the high mass range for chaetoconvosins A and B are formed with the loss of H O, CO, or both. The neutral loss of CH NCO can be detected for chaetoconvosin B. However, their fragmentation patterns producing product ions in the low mass range vary greatly. It was found that hydroxyl or H atom linked to C1 is the key leading to the fragmentation differences. McLafferty-type rearrangement (producing the characteristic product ion at m/z 155), four-centered H rearrangement (generating m/z 193), and RDA reaction (producing m/z 203) are directly or indirectly related to the groups linked to C1. The identity of major product ions was supported by a D-labeling experiment. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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189. Actin Disorganization Plays a Vital Role in Impaired Embryonic Development of In Vitro-Produced Mouse Preimplantation Embryos.
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Tan, Kun, An, Lei, Wang, Shu-Min, Wang, Xiao-Dong, Zhang, Zhen-Ni, Miao, Kai, Sui, Lin-Lin, He, Shu-Zhi, Nie, Jing-Zhou, Wu, Zhong-Hong, and Tian, Jian-Hui
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HUMAN embryology , *REPRODUCTIVE technology , *INFERTILITY , *BLASTOCYST , *CYTOCHALASINS , *GENE expression - Abstract
Assisted reproductive technology (ART) is being increasingly applied to overcome infertility. However, the in vitro production process, the main procedure of ART, can lead to aberrant embryonic development and health-related problems in offspring. Understanding the mechanisms underlying the ART-induced side effects is important to improve the ART process. In this study, we carried out comparative transcriptome profiling between in vivo- (IVO) and in vitro- produced (IVP) mouse blastocysts. Our results suggested that aberrant actin organization might be a major factor contributing to the impaired development of IVP embryos. To test this, we examined the effect of actin disorganization on the development of IVP preimplantation embryos. Specific disruption of actin organization by cytochalasin B (CB) indicated that well-organized actin is essential for in vitro embryonic development. Supplementing the culture medium with 10–9 M melatonin, a cytoskeletal modulator in adult somatic cells, significantly reversed the disrupted expression patterns of genes related to actin organization, including Arhgef2, Bcl2, Coro2b, Flnc, and Palld. Immunofluorescence analysis showed that melatonin treatment of IVP embryos significantly improved the distribution and organization of actin filaments (F-actin) from the 8-cell stage onwards. More importantly, we found that melatonin alleviated the CB-mediated aberrant F-actin distribution and organization and rescued CB-induced impaired embryonic development. This is the first study to indicate that actin disorganization is implicated in impaired development of IVP embryos during the preimplantation stage. We also demonstrated that improving actin organization is a promising strategy to optimize existing IVP systems. [ABSTRACT FROM AUTHOR]
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- 2015
- Full Text
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190. Effects of isoflurane and sevoflurane on the neutrophil myeloperoxidase system of horses.
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Minguet, Grégory, Franck, Thierry, Joris, Jean, Ceusters, Justine, Mouithys-Mickalad, Ange, Serteyn, Didier, and Sandersen, Charlotte
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ISOFLURANE , *SEVOFLURANE , *MYELOPEROXIDASE , *CYTOCHALASINS , *HORSE diseases , *ENZYME-linked immunosorbent assay , *NEUTROPHILS , *OXIDATIVE stress - Abstract
Volatile anaesthestics have shown to modulate the oxidative response of polymorphonuclear neutrophils (PMNs). We investigated the effects of isoflurane and sevoflurane on the degranulation of total and active myeloperoxidase (MPO) from horse PMNs and their direct interaction with MPO activity. Whole blood from horse was incubated in 1 and 2 minimal alveolar concentrations (MAC) of isoflurane or sevoflurane for 1 h and PMNs were stimulated with cytochalasin B (CB) plus N-formyl-méthionyl-leucyl-phenylalanine (fMLP). After stimulation, the plasma was collected to measure total and active MPO by enzyme-linked immunosorbent assay (ELISA) and specific immunological extraction followed by enzymatic detection (SIEFED) respectively. The effects of 1 and 2 MAC of isoflurane and sevoflurane on the peroxidase and chlorination activity of pure MPO were assessed by fluorescence using Amplex red and 3′-(p-aminophenyl) fluorescein (APF) respectively and in parallel with a SIEFED assay to estimate the potential interaction of the anaesthetics with the enzyme. Although isoflurane and sevoflurane had inconsistent effects on total MPO release, both volatile agents reduced active MPO release and showed a direct inhibition on the peroxidase and the chlorination activity of the enzyme. A persistent interaction between MPO and anaesthetics was evidenced with isoflurane but not with sevoflurane. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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191. Cytochalasin derivatives from a jellyfish-derived fungus Phoma sp.
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Kim, Eun La, Wang, Haibo, Park, Ju Hee, Hong, Jongki, Choi, Jae Sue, Im, Dong Soon, Chung, Hae Young, and Jung, Jee H.
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CYTOCHALASINS , *STEREOCHEMISTRY , *TUMORS , *CELL lines , *DOXORUBICIN , *DRUG efficacy , *TUMOR treatment - Abstract
Four new cytochalasin derivatives ( 1 – 4 ), together with proxiphomin ( 5 ), were isolated from a jellyfish-derived fungus Phoma sp. The planar structures and relative stereochemistry were established by analysis of 1D and 2D NMR data. The absolute configuration was defined by the modified Mosher’s method. The compounds showed moderate cytotoxicity against a small panel of human solid tumor cell lines (A549, KB, and HCT116). [ABSTRACT FROM AUTHOR]
- Published
- 2015
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192. Armochaetoglobins K-R, Anti-HIV Pyrrole-Based Cytochalasans from Chaetomium globosum TW1-1.
- Author
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Chen, Chunmei, Zhu, Hucheng, Wang, Jianping, Yang, Jing, Li, Xiao‐Nian, Wang, Jing, Chen, Keliang, Wang, Yanyan, Luo, Zengwei, Yao, Guangmin, Xue, Yongbo, and Zhang, Yonghui
- Subjects
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CYTOCHALASINS , *CHAETOMIUM globosum , *ARMADILLIDIUM vulgare , *SPECTRUM analysis , *X-ray diffraction , *CIRCULAR dichroism , *PYRROLES - Abstract
Eight rare pyrrole-based cytochalasans, termed armochaetoglobins K-R ( 1- 8), along with three known analogues ( 9- 11), were isolated from the solid culture broth of Chaetomium globosum TW1-1, a symbiotic fungus derived from the medicinal terrestrial arthropod Armadillidium vulgare. Their structures were elucidated using a combination of spectroscopic analysis, a single-crystal X-ray diffraction experiment, and an electronic circular dichroism (ECD) calculation. Compounds 4- 8 represent the first examples of chaetoglobosin-type cytochalasans with an sp3 methine carbon at C-18. All of the isolates were evaluated for their anti-HIV activities in vitro, and compounds 2- 4, 7, 8, and 10 showed significant anti-HIV activities, with EC50 values ranging from 0.11 to 0.55 μ M, and selectivity index (SI) values ranging from 12.33 to 75.42. A plausible biosynthetic pathway was proposed to explain the origin of the pyrrole ring. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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193. Effect of Culture Conditions on Metabolite Production of Xylaria sp.
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Hongqi Zhang, Zhangshuang Deng, Zhiyong Guo, Yan Peng, Nianyu Huang, Haibo He, Xuan Tu, and Kun Zou
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XYLARIA , *NATURAL products , *CYTOCHALASINS , *PLANT metabolites , *CELL-mediated cytotoxicity - Abstract
Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1-5 to six new α-pyrone derivatives, xylapyrones A-F (compounds 6-11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1-3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC50 values ranging from 25 to 63 μM and compounds 4-11 were found to be inactive, with ICY50 values >100 μM. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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194. New cytochalasins from medicinal macrofungus Crodyceps taii and their inhibitory activities against human cancer cells.
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Li, Xiao-Gang, Pan, Wei-Dong, Lou, Hua-Yong, Liu, Ru-Ming, Xiao, Jian-Hui, and Zhong, Jian-Jiang
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CYTOCHALASINS , *MEDICINAL plants , *MACROFUNGI , *CANCER cells , *CORDYCEPS - Abstract
Three new cytochalasins ( 1 – 3 ) together with two known cytochalasin analogues ( 4 and 5 ) were isolated from the chloroform fraction of ethanolic extract of a medicinal macrofungus Cordyceps taii . The structures of the new compounds were elucidated on the basis of spectroscopic analysis, including HRESIMS, 1D and 2D NMR experiments. The cytotoxicities of Compounds 1 – 5 were investigated by the sulforhodamine B (SRB) method in vitro against human highly metastatic lung cancer cell 95-D, human lung cancer cell line A-549 and normal hepatocyte HL-7702. The results revealed that Compounds 4 and 5 showed potent antitumor activities against human lung cancer cell 95-D with IC 50 value of 3.67 and 4.04 μM, respectively. In comparison with cisplatin, the first-line chemotherapy drug, they had little or no cytotoxicity on normal cells, but showed stronger cytotoxic effects on cancer cells 95-D. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
195. New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum avicennae: Effects on Neutrophil Pro-Inflammatory Responses.
- Author
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Jih-Jung Chen, Chieh-Kai Yang, Yueh-Hsiung Kuo, Tsong-Long Hwang, Wen-Lung Kuo, Yun-Ping Lim, Ping-Jyun Sung, Tsung-Hsien Chang, and Ming-Jen Cheng
- Subjects
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ZANTHOXYLUM , *COUMARIN derivatives , *NEUTROPHILS , *PHENYLALANINE , *CYTOCHALASINS , *INFLAMMATION treatment , *BARK - Abstract
Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4-18). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory concentration (IC50) values ≤7.65 μg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-Lleucyl- L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited fMLP/CB-induced elastase release with IC50 values ≤8.17 μg/mL. This investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
196. Secondary Metabolites Produced by Phomopsis sp. 11F0023, an Endophytic Fungus in Eragrostis amabilis.
- Author
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Cheng, Ming-Jen, Wu, Ming-Der, Chan, Hing-Yuen, Hsieh, Sung-Yuan, Chen, Yen-Lin, Chen, Ih-Sheng, Chan, Fu-Ling, Chen, Jih-Jung, and Yuan, Gwo-Fang
- Subjects
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METABOLITES , *PHOMOPSIS , *LOVE grass , *CYTOCHALASINS , *ANTIBIOTICS , *HETEROCYCLIC compounds - Abstract
Chemical investigation of the n-butanol-soluble layer of the MeOH extract of rice fermented with one endophytic fungal strain, Phomopsis sp. 11F0023, led to isolation of one new butenolide compound, namely phomobutenolide ( 1), together with three known compounds, ergosta-4,6,8(14),22-tetraen-3-one ( 2), cytochalasin H ( 3), and cytochalasin J ( 4). This strain was isolated from leaves of the species Eragrostis amabilis (L.) Wight & Arn., collected in the 19 Hectares Grassland Area, Siangshan District, Hsinchu City, Taiwan. Their structures were elucidated by spectroscopic analyses, including H and C NMR, 2D NMR (HSQC, HMBC, COSY, and NOESY), and HR-ESI-MS. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
197. Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels.
- Author
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Gnanasambandam, Radhakrishnan, Bae, Chilman, Gottlieb, Philip A., and Sachs, Frederick
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ION channels , *PERMEABILITY , *ORGANIC cation transporters , *MONOVALENT cations , *CYTOCHALASINS , *POTASSIUM channels - Abstract
Members of the eukaryotic PIEZO family (the human orthologs are noted hPIEZO1 and hPIEZO2) form cation-selective mechanically-gated channels. We characterized the selectivity of human PIEZO1 (hPIEZO1) for alkali ions: K+, Na+, Cs+ and Li+; organic cations: TMA and TEA, and divalents: Ba2+, Ca2+, Mg2+ and Mn2+. All monovalent ions permeated the channel. At a membrane potential of -100 mV, Cs+, Na+ and K+ had chord conductances in the range of 35–55 pS with the exception of Li+, which had a significantly lower conductance of ~ 23 pS. The divalents decreased the single-channel permeability of K+, presumably because the divalents permeated slowly and occupied the open channel for a significant fraction of the time. In cell-attached mode, 90 mM extracellular divalents had a conductance for inward currents carried by the divalents of: 25 pS for Ba2+ and 15 pS for Ca2+ at -80 mV and 10 pS for Mg2+ at -50 mV. The organic cations, TMA and TEA, permeated slowly and attenuated K+ currents much like the divalents. As expected, the channel K+ conductance increased with K+ concentration saturating at ~ 45 pS and the KD of K+ for the channel was 32 mM. Pure divalent ion currents were of lower amplitude than those with alkali ions and the channel opening rate was lower in the presence of divalents than in the presence of monovalents. Exposing cells to the actin disrupting reagent cytochalasin D increased the frequency of openings in cell-attached patches probably by reducing mechanoprotection. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
198. Recovery of Aging-Related Size Increase of Skin Epithelial Cells: In vivo Mouse and In vitro Human Study.
- Author
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Sokolov, Igor, Guz, Natali V., Iyer, Swaminathan, Hewitt, Amy, Sokolov, Nina A., Erlichman, Joseph S., and Woodworth, Craig D.
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CELLULAR aging , *EPITHELIAL cells , *CYTOCHALASINS , *GROWTH factors , *IN vitro studies , *LABORATORY mice - Abstract
The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro. Six nude mice were treated by topical application of cytochalasin B on skin of the dorsal left midsection for 140 days (the right side served as control for placebo treatment). An average decrease in cell size of 56±16% resulted. A reduction of cell size was also observed on primary human skin epithelial cells of different in vitro age (passages from 1 to 8). A cell strain obtained from a pool of 6 human subjects was treated with cytochalasin B in vitro for 12 hours. We observed a decrease in cell size that became statistically significant and reached 20–40% for cells of older passage (6–8 passages) whereas no substantial change was observed for younger cells. These results may be important for understanding the aging processes, and for cosmetic treatment of aging skin. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
199. Diversely Functionalised Cytochalasins through Mutasynthesis and Semi-Synthesis
- Author
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Wang, Chongqing, Lambert, Christopher, Hauser, Maurice, Deuschmann, Adrian, Zeilinger, Carsten, Rottner, Klemens, Stradal, Theresia E. B., Stadler, Marc, Skellam, Elizabeth J., Cox, Russell J., Wang, Chongqing, Lambert, Christopher, Hauser, Maurice, Deuschmann, Adrian, Zeilinger, Carsten, Rottner, Klemens, Stradal, Theresia E. B., Stadler, Marc, Skellam, Elizabeth J., and Cox, Russell J.
- Abstract
Mutasynthesis of pyrichalasin H from Magnaporthe grisea NI980 yielded a series of unprecedented 4′-substituted cytochalasin analogues in titres as high as the wild-type system (≈60 mg L−1). Halogenated, O-alkyl, O-allyl and O-propargyl examples were formed, as well as a 4′-azido analogue. 4′-O-Propargyl and 4′-azido analogues reacted smoothly in Huisgen cycloaddition reactions, whereas p-Br and p-I compounds reacted in Pd-catalysed cross-coupling reactions. A series of examples of biotin-linked, dye-linked and dimeric cytochalasins was rapidly created. In vitro and in vivo bioassays of these compounds showed that the 4′-halogenated and azido derivatives retained their cytotoxicity and antifungal activities; but a unique 4′-amino analogue was inactive. Attachment of larger substituents attenuated the bioactivities. In vivo actin-binding studies with adherent mammalian cells showed that actin remains the likely intracellular target. Dye-linked compounds revealed visualisation of intracellular actin structures even in the absence of phalloidin, thus constituting a potential new class of actin-visualisation tools with filament-barbed end-binding specificity.
- Published
- 2020
200. Profilin-1 Serves as a Gatekeeper for Actin Assembly by Arp2/3-Dependent and -Independent Pathways.
- Author
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Rotty, Jeremy D., Wu, Congying, Haynes, Elizabeth M., Suarez, Cristian, Winkelman, Jonathan D., Johnson, Heath E., Haugh, Jason M., Kovar, David R., and Bear, James E.
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PROFILIN , *CELL culture , *LAMELLIPODIA , *CELL migration , *CYTOCHALASINS - Abstract
Summary Cells contain multiple F-actin assembly pathways, including the Arp2/3 complex, formins, and Ena/VASP, which have largely been analyzed separately. They collectively generate the bulk of F-actin from a common pool of G-actin; however, the interplay and/or competition between these pathways remains poorly understood. Using fibroblast lines derived from an Arpc2 conditional knockout mouse, we established matched-pair cells with and without the Arp2/3 complex. Arpc2 −/− cells lack lamellipodia and migrate more slowly than WT cells but have F-actin levels indistinguishable from controls. Actin assembly in Arpc2 −/− cells was resistant to cytochalasin-D and was highly dependent on profilin-1 and Ena/VASP but not formins. Profilin-1 depletion in WT cells increased F-actin and Arp2/3 complex in lamellipodia. Conversely, addition of exogenous profilin-1 inhibited Arp2/3 complex actin nucleation in vitro and in vivo. Antagonism of the Arp2/3 complex by profilin-1 in cells appears to maintain actin homeostasis by balancing Arp2/3 complex-dependent and -independent actin assembly pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
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