scholarly journals Myosin 1b functions as an effector of EphB signaling to control cell repulsion

2015 ◽  
Vol 210 (2) ◽  
pp. 347-361 ◽  
Author(s):  
Marie-Thérèse Prospéri ◽  
Priscilla Lépine ◽  
Florent Dingli ◽  
Perrine Paul-Gilloteaux ◽  
René Martin ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Morphological Changes ◽  
Control Cell ◽  
Dependent Manner ◽  
Eph Receptors ◽  
Actin Remodeling ◽  
Actin Cortex ◽  
Cell Segregation ◽  
Tethered Ligands ◽  
Cell Repulsion

Eph receptors and their membrane-tethered ligands, the ephrins, have important functions in embryo morphogenesis and in adult tissue homeostasis. Eph/ephrin signaling is essential for cell segregation and cell repulsion. This process is accompanied by morphological changes and actin remodeling that drives cell segregation and tissue patterning. The actin cortex must be mechanically coupled to the plasma membrane to orchestrate the cell morphology changes. Here, we demonstrate that myosin 1b that can mechanically link the membrane to the actin cytoskeleton interacts with EphB2 receptors via its tail and is tyrosine phosphorylated on its tail in an EphB2-dependent manner. Myosin 1b regulates the redistribution of myosin II in actomyosin fibers and the formation of filopodia at the interface of ephrinB1 and EphB2 cells, which are two processes mediated by EphB2 signaling that contribute to cell repulsion. Together, our results provide the first evidence that a myosin 1 functions as an effector of EphB2/ephrinB signaling, controls cell morphology, and thereby cell repulsion.

scholarly journals Leptin affects filopodia and cofilin in NK-92 cells in a dose- and time-dependent manner

2018 ◽  
Author(s):  
Jana Oswald ◽  
Maximilian Büttner ◽  
Simon Jasinski-Bergner ◽  
Roland Jacobs ◽  
Philip Rosenstock ◽  
...  
Keyword(s):  
Nk Cells ◽  
Morphological Changes ◽  
Cellular Migration ◽  
Time Dependent ◽  
Dependent Manner ◽  
Actin Remodeling ◽  
Dependent Activity ◽  
Time Dependent Effect ◽  
In Vitro Effects

Hyperleptinemia, associated with obesity, is related with immune dysfunction and carcinogenesis. Natural Killer (NK) cells, a major component of the innate immune system are mediators of anti-tumor immunity and the most actively migrating cells among leukocytes. Actin rearrangement, promoted by cofilin plays a central role in cellular migration. Leptin affects the phosphorylation-dependent activity of cofilin and thus actin remodeling. We used human NK-92 cells to explore the in vitro effects of leptin on co-localization of cofilin and F-actin and on morphological changes in NK cells. NK-92 cells were incubated with different leptin concentrations (10 and 100 ng/mL) for 30 min and 24 h and immunocytochemically stained. Results demonstrate a dose- and time-dependent influence of leptin on cellular morphology. Utilizing confocal microscopy, we observed that the co-localization of cofilin-1 and F-actin was slightly influenced by leptin. In summary, the present study demonstrates an impact of a physiological leptin stimulation on the filopodia length, and a time-dependent effect on the co-localization of cofilin and F-actin in NK-92 cells. 

scholarly journals Functional Fibronectin Adsorption on Aptamer-Doped Chitosan Modulates Cell Morphology by Integrin-Mediated Pathway

Materials ◽  
2019 ◽  
Vol 12 (5) ◽  
pp. 812 ◽  
Author(s):  
Ludovica Parisi ◽  
Andrea Toffoli ◽  
Massimiliano G. Bianchi ◽  
Carlo Bergonzi ◽  
Annalisa Bianchera ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Actin Polymerization ◽  
Control Cell ◽  
Material Surface ◽  
Dependent Manner ◽  
Promote Cell Proliferation ◽  
Fine Control ◽  
Dose Dependent ◽  
Insight Into ◽  
Control Protein

A decisive step in cell-biomaterial interaction is represented by the adsorption of proteins at the interface, whose fine control may be useful to trigger proper cell response. To this purpose, we can selectively control protein adsorption on biomaterials by means of aptamers. Aptamers selected to recognize fibronectin dramatically enhance chitosan ability to promote cell proliferation and adhesion, but the underlying biological mechanism remains unknown. We supposed that aptamers contributed to ameliorate the adsorption of fibronectin in an advantageous geometrical conformation for cells, thus regulating their morphology by the proper activation of the integrin-mediated pathway. We investigated this possibility by culturing epithelial cells on chitosan enriched with increasing doses of aptamers in the presence or in the absence of cytoskeleton pharmacological inhibitors. Our results showed that aptamers control cell morphology in a dose dependent manner (p < 0.0001). Simultaneously, when the inhibition of actin polymerization was induced, the control of cell morphology was attenuated (p < 0.0001), while no differences were detected when cells contractility was challenged (p > 0.05). Altogether, our data provide evidence that aptamers contribute to control fibronectin adsorption on biomaterials by preserving its conformation and thus function. Furthermore, our work provides a new insight into a new way to accurately tailor material surface bioactivity.

scholarly journals RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ying-Ying Liang ◽  
Xu-Bin Deng ◽  
Xian-Tao Lin ◽  
Li-Li Jiang ◽  
Xiao-Ting Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Transcriptional Coactivator ◽  
Actin Remodeling ◽  
Aggressive Tumor ◽  
Subunit B

Abstract Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

Docosahexaenoic Acid, a Peroxisome Proliferator-Activated Receptor-α Activator, Induces Apoptosis in Vascular Smooth Muscle Cells by Activation of P38 Mitogen-Activated Protein Kinase

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 679-679
Author(s):  
Quy N Diep ◽  
Rhian M Touyz ◽  
Ernesto L Schiffrin
Keyword(s):  
Smooth Muscle ◽  
Cytochrome C ◽  
Docosahexaenoic Acid ◽  
Vascular Smooth Muscle ◽  
Morphological Changes ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Mitogen Activated Protein ◽  
P38 Mapks

9 Omega-3 fatty acids (n-3 FAs) exert a blood pressure-lowering effect in hypertension, possibly by influencing vascular structure. We previously demonstrated that n-3 FAs might induce vascular smooth muscle cell (VSMC) apoptosis, which could exert an effect on structure of blood vessels. This study investigated signaling pathways through which n-3 FAs mediate apoptosis in VSMCs. Cultured Mesenteric VSMCs from Sprague Dawley rats were stimulated with docosahexaenoic acid (DHA), a representative n-3 FA. Morphological changes of apoptosis and DNA fragmentation were examined by phase-contrast microscopy and fluorescence microscopy with Hoechst 33342 staining. To clarify possible pathways of apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (p38 MAPKs), bax, bcl-2, cytochrome C and peroxisome proliferator-activated receptors-α (PPARs-α) was evaluated by Western blot analysis. DHA treatment induced cell shrinkage, cell membrane blebbing and apoptotic bodies in VSMCs. DHA increased apoptosis (%) in a time-dependent manner to 1.5±0.1, 3.6±0.5, 7.1±0.4, 22.5±0.6, 50.8±1.8 and 61.4±0.9 after 0, 1, 3, 6, 17, and 24 h, respectively. DHA time-dependently activated p38 MAPKs, bax, PPARs-α and cytochrome C with maximal effects obtained after 5, 30 min, 1 h and 3 h, respectively to 551±42, 245±55, 310±12 and 407±14.7 % of controls, respectively. SB-203580 (10 -5 M) and SB-202190 (10 -5 M), selective p38 inhibitors, reduced DHA-elicited apoptosis and expression of PPARs-α, but had no effect on expression of bax or cytochrome C. The present results indicate that DHA induces apoptosis in VSMCs through at least two distinct mechanisms: (i) a p38-dependent pathway that regulates PPAR-α and (ii) a p38-independent pathway via dissipation of mitochondrial transmembrane potential. The death-signaling pathway mediated by DHA may involve an integration of these multiple pathways. By triggering VSMC apoptosis, DHA could play a pathophysiological role in vascular remodeling in cardiovascular disease.

Effect of methyl farnesoate and farnesoic acid during 5th zoea and megalopa metamorphosis in the mud crab Scylla paramamosain Estampador, 1950 (Decapoda, Brachyura, Portunidae)

Crustaceana ◽  
2021 ◽  
Vol 94 (7) ◽  
pp. 855-863
Author(s):  
Ming Zhao ◽  
Fengying Zhang ◽  
Wei Wang ◽  
Zhiqiang Liu ◽  
Lingbo Ma
Keyword(s):  
Larval Development ◽  
Morphological Changes ◽  
Scylla Paramamosain ◽  
Dependent Manner ◽  
Mud Crab ◽  
Methyl Farnesoate ◽  
Concentration Dependent Manner ◽  
Low Levels ◽  
Juvenile Crab ◽  
Farnesoic Acid

Abstract The mud crab Scylla paramamosain is one of the economically important aquaculture species in China. The larval development of the mud crab is characterized by two significant morphological changes, from the 5th zoea (Z5) to the megalopa (M) stage and from the M to the first juvenile crab (C1) stage. In this study, we found that methyl farnesoate (MF) could prohibit the Z5 to M metamorphosis in a concentration-dependent manner, and that a concentration of 10 μM MF could completely prohibit the Z5 metamorphosis. Farnesoic acid (FA) could also prohibit the Z5 metamorphosis, but its effects seemed to be concentration-independent. In addition, MF could delay rather than prohibit the M to C1 metamorphosis, while FA had no effect on the M to C1 metamorphosis at all. To summarize, it is hypothesized that either absence of MF and FA, or at least very low levels of these substances, might be necessary for a successful Z5 to M metamorphosis.

scholarly journals Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wai Kuan Yong ◽  
Sri Nurestri Abd Malek
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Morphological Changes ◽  
S Phase ◽  
Phase Cell ◽  
Cervical Cancer Cell Line ◽  
Dependent Manner ◽  
Cervical Cancer Cells

We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.

scholarly journals Cinobufacini from the Skin of Bufo bufo gargarizans Induces Apoptosis, Possibly via Activation of the Wnt/β-Catenin Pathway, in Human Osteosarcoma Cells

2018 ◽  
Vol 13 (2) ◽  
pp. 1934578X1801300
Author(s):  
Xiu-cai Ma ◽  
Hui-qiang Ding ◽  
Jian-dang Shi ◽  
Long Hei ◽  
Ning-kui Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Morphology ◽  
Bufo Bufo ◽  
Tunel Staining ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Bufo Gargarizans ◽  
Human Osteosarcoma Cells ◽  
Induced Apoptosis ◽  
Related Proteins

Cinobufacini (huachansu) is a traditional Chinese medicine extracted from the skin of Bufo bufo gargarizans, which is used in clinical cancer therapy. The purpose of this study was to investigate the signaling pathways regulating cinobufacini-induced apoptosis in the osteosarcoma cell line, U2OS. We used 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the effects of cinobufacini on cell proliferation in U2OS cells. Changes in cell morphology and apoptosis were detected by TUNEL staining. The expression of apoptosis-related and Wnt/β-catenin pathway proteins was detected by immunofluorescence, RT-PCR, and western blot analysis. Our data indicated that cinobufacini significantly inhibited cell proliferation in a dose- and time-dependent manner. Marked changes in cell morphology and apoptosis rate were clearly observed after cinobufacini treatment. The Wnt/β-catenin pathway was activated, and β-catenin expression was positive in cells after treatment. Further, protein expression of bax was increased, whereas bcl-2 was decreased, resulting in an increased bax/bcl-2 ratio. Moreover, after cinobufacini treatment, the expression of Wnt/β-catenin pathway-related proteins was similar to controls. Taken together, our study indicates that cinobufacini can induce apoptosis in U2OS cells, likely through activating the Wnt/β-catenin pathway.

scholarly journals Use of a model to understand the synergies underlying the antibacterial mechanism of H2O2-producing honeys

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Masoura ◽  
Paolo Passaretti ◽  
Tim W. Overton ◽  
Pete A. Lund ◽  
Konstantinos Gkatzionis
Keyword(s):  
Gluconic Acid ◽  
Morphological Changes ◽  
Dependent Manner ◽  
Antibacterial Mechanism ◽  
General Stress Response ◽  
E Coli ◽  
Simple Model System ◽  
Ancient Times ◽  
K 12 ◽  
Dose Dependent

Abstract Honey has been valued as a powerful antimicrobial since ancient times. However, the understanding of the underlying antibacterial mechanism is incomplete. The complexity and variability of honey composition represent a challenge to this scope. In this study, a simple model system was used to investigate the antibacterial effect of, and possible synergies between, the three main stressors present in honey: sugars, gluconic acid, and hydrogen peroxide (H2O2), which result from the enzymatic conversion of glucose on honey dilution. Our results demonstrated that the synergy of H2O2 and gluconic acid is essential for the antibacterial activity of honey. This synergy caused membrane depolarization, destruction of the cell wall, and eventually growth inhibition of E. coli K-12. The presence of H2O2 stimulated the generation of other long-lived ROS in a dose-dependent manner. Sugars caused osmosis-related morphological changes, however, decreased the toxicity of the H2O2/gluconic acid. The susceptibility of catalase and general stress response sigma factor mutants confirmed the synergy of the three stressors, which is enhanced at higher H2O2 concentrations. By monitoring cellular phenotypic changes caused by model honey, we explained how this can be bactericidal even though the antimicrobial compounds which it contains are at non-inhibitory concentrations.

scholarly journals Antimicrobial functional divergence of the cecropin antibacterial peptide gene family in Musca domestica

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Peng ◽  
Zhaoying Wu ◽  
Weiwei Liu ◽  
Huiling Long ◽  
Guiming Zhu ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Musca Domestica ◽  
Morphological Changes ◽  
Functional Divergence ◽  
Membrane Integrity ◽  
Gram Negative Bacteria ◽  
Dependent Manner ◽  
Antibacterial Effects ◽  
Gram Negative ◽  
Absorbing Material

Abstract Background It has been reported that there are more than ten antimicrobial peptides (AMPs) belonging to the cecropin family in Musca domestica; however, few of them have been identified, and the functions of the other molecules are poorly understood. Methods Sequences of the M. domestica cecropin family of genes were cloned from cDNA template, which was reverse-transcribed from total mRNA isolated from third-instar larvae of M. domestica that were challenged with pathogens. Sequence analysis was performed using DNAMAN comprehensive analysis software, and a molecular phylogenetic tree of the cecropin family was constructed using the Neighbour-Joining method in MEGA v.5.0 according to the mature peptide sequences. Antibacterial activity of the synthetic M. domestica cecropin protein was detected and the minimum inhibitory concentration (MIC) values were determined using broth microdilution techniques. Time-killing assays were performed on the Gram-negative bacteria, Acinetobacter baumannii, at the logarithmic or stabilizing stages of growth, and its morphological changes when treated with Cec4 were assessed by scanning electron microscopy (SEM) and detection of leakage of 260 nm absorbing material. Results Eleven cecropin family genes, namely Cec01, Cec02 and Cec1-9, show homology to the Cec form in a multigene family on the Scaffold18749 of M. domestica. In comparing the encoded cecropin protein sequences, most of them have the basic characteristics of the cecropin family, containing 19 conservative amino acid residues. To our knowledge, this is the first experimental demonstration that most genes in the Cec family are functional. Cec02, Cec1, Cec2, Cec5 and Cec7 have similar antibacterial spectra and antibacterial effects against Gram-negative bacteria, while Cec4 displays a more broad-spectrum of antimicrobial activity and has a very strong effect on A. baumannii. Cec4 eliminated A. baumannii in a rapid and concentration-dependent manner, with antibacterial effects within 24 h at 1× MIC and 2× MIC. Furthermore, SEM analysis and the leakage of 260 nm absorbing material detection indicated that Cec4 sterilized the bacteria through the disruption of cell membrane integrity. Conclusions Although there are more than ten cecropin genes related to M. domestica, some of them have no preferred antibacterial activity other than Cec4 against A. baumannii.

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