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https://www.readbyqxmd.com/read/28639351/titanium-released-from-dental-implant-enhances-pre-osteoblast-adhesion-by-ros-modulating-crucial-intracellular-pathways
#1
M C Rossi, Fjb Bezerra, R A Silva, B P Crulhas, Cjc Fernandes, A S Nascimento, V A Pedrosa, P Padilha, W F Zambuzzi
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p<0...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28636918/actin-filament-strain-promotes-severing-and-cofilin-dissociation
#2
Anthony C Schramm, Glen M Hocky, Gregory A Voth, Laurent Blanchoin, Jean-Louis Martiel, Enrique M De La Cruz
Computational and structural studies have been indispensable in investigating the molecular origins of actin filament mechanical properties and modulation by the regulatory severing protein cofilin. All-atom molecular dynamics simulations of cofilactin filament structures determined by electron cryomicroscopy reveal how cofilin enhances the bending and twisting compliance of actin filaments. Continuum mechanics models suggest that buckled cofilactin filaments localize elastic energy at boundaries between bare and cofilin-decorated segments because of their nonuniform elasticity, thereby accelerating filament severing...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#3
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28625781/adf-cofilin-accelerates-actin-dynamics-by-severing-filaments-and-promoting-their-depolymerization-at-both-ends
#4
Hugo Wioland, Berengere Guichard, Yosuke Senju, Sarah Myram, Pekka Lappalainen, Antoine Jégou, Guillaume Romet-Lemonne
Actin-depolymerizing factor (ADF)/cofilins contribute to cytoskeletal dynamics by promoting rapid actin filament disassembly. In the classical view, ADF/cofilin sever filaments, and capping proteins block filament barbed ends whereas pointed ends depolymerize, at a rate that is still debated. Here, by monitoring the activity of the three mammalian ADF/cofilin isoforms on individual skeletal muscle and cytoplasmic actin filaments, we directly quantify the reactions underpinning filament severing and depolymerization from both ends...
June 14, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28625780/enhanced-depolymerization-of-actin-filaments-by-adf-cofilin-and-monomer-funneling-by-capping-protein-cooperate-to-accelerate-barbed-end-growth
#5
Shashank Shekhar, Marie-France Carlier
A living cell's ability to assemble actin filaments in intracellular motile processes is directly dependent on the availability of polymerizable actin monomers, which feed polarized filament growth [1, 2]. Continued generation of the monomer pool by filament disassembly is therefore crucial. Disassemblers like actin depolymerizing factor (ADF)/cofilin and filament cappers like capping protein (CP) are essential agonists of motility [3-8], but the exact molecular mechanisms by which they accelerate actin polymerization at the leading edge and filament turnover has been debated for over two decades [9-12]...
June 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28608282/poly-adp-ribosylated-proteins-in-mononuclear-cells-from-patients-with-type-2-diabetes-identified-by-proteomic-studies
#6
Alessandra Giorgi, Italo Tempera, Giorgia Napoletani, Diego Drovandi, Cinzia Potestà, Sara Martire, Elisabetta Mandosi, Tiziana Filardi, M Eugenia Schininà, Susanna Morano, Maria d'Erme, Bruno Maras
AIMS: In diabetes, hyperglycemia increases reactive oxygen species that induce DNA damage and poly(ADP-ribose)polymerase activation. The aim of this study is to characterize the proteomic profile and the role of poly(ADP-ribosylation) in patients with type 2 diabetes. METHODS: A proteomic platform based on 2DE and MALDI-ToF spectrometry was applied to peripheral blood mononuclear cells obtained from two different cohorts in which diabetic (n = 14) and normoglycemic patients (n = 11) were enrolled...
June 12, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28599494/cucurbitacin-e-induces-apoptosis-of-human-prostate-cancer-cells-via-cofilin-1-and-mtorc1
#7
Xiaolong He, Qi Gao, Yayong Qiang, Wei Guo, Yadong Ma
Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598765/shigella-depends-on-sepa-to-destabilize-the-intestinal-epithelial-integrity-via-cofilin-activation
#8
Ana Maldonado-Contreras, James R Birtley, Erik Boll, Yun Zhao, Karen L Mumy, Juan Toscano, Seyoum Ayehunie, Hans-Christian Reinecker, Lawrence J Stern, Beth A McCormick
Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions...
June 9, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28588454/reelin-signaling-inactivates-cofilin-to-stabilize-the-cytoskeleton-of-migrating-cortical-neurons
#9
REVIEW
Michael Frotscher, Shanting Zhao, Shaobo Wang, Xuejun Chai
Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28588038/the-amp-related-kinase-ampk-induces-ca-2-independent-dilation-of-resistance-arteries-by-interfering-with-actin-filament-formation
#10
Kai M Schubert, Jiehua Qiu, Stephanie Blodow, Margarethe Wiedenmann, Lubomir T Lubomirov, Gabriele Pfitzer, Ulrich Pohl, Holger Schneider
Rationale: Decreasing Ca(2+) sensitivity of vascular smooth muscle (VSM) allows for vasodilation without lowering of cytosolic Ca(2+) This may be particularly important in states requiring maintained dilation such as hypoxia. AMPK is an important cellular energy sensor in VSM. Regulation of Ca(2+) sensitivity usually is attributed to myosin light chain phosphatase (MLCP) activity but findings in non-VSM identified changes in the actin cytoskeleton. The potential role of AMPK in this setting is widely unknown...
June 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28586109/fyn-kinase-mediates-cortical-actin-ring-depolymerization-required-for-mast-cell-migration-in-response-to-tgf-%C3%AE-in-mice
#11
Karla A Ramírez-Valadez, Genaro Vázquez-Victorio, Marina Macías-Silva, Claudia González-Espinosa
Transforming Growth Factor-β (TGF-β) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-β-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-β-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-β was impaired in the absence of the kinase...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28573459/cytoskeleton-associated-risk-modifiers-involved-in-early-and-rapid-progression-of-sporadic-creutzfeldt-jakob-disease
#12
Saima Zafar, Neelam Younas, Nadeem Sheikh, Waqas Tahir, Mohsin Shafiq, Matthias Schmitz, Isidre Ferrer, Olivier Andréoletti, Inga Zerr
A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. In this study, we demonstrate the pre-symptomatic dysregulation of cytoskeleton assembly and its associated cofilin-1 pathway in strain and brain region-specific manners in MM1 and VV2 subtype-specific Creutzfeldt-Jakob disease at clinical and pre-clinical stage. At physiological level, PrP(C) interaction with cofilin-1 and phosphorylated form of cofilin (p-cofilin(Ser3)) was investigated in primary cultures of mouse cortex neurons (PCNs) of PrP(C) wild-type and knockout mice (PrP(-/-))...
June 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28554775/zonula-occludens-2-regulates-rho-proteins-activity-and-the-development-of-epithelial-cytoarchitecture-and-barrier-function
#13
Arturo Raya-Sandino, Alejandro Castillo-Kauil, Alaide Domínguez-Calderón, Lourdes Alarcón, David Flores-Benitez, Francisco Cuellar-Perez, Bruno López-Bayghen, Bibiana Chávez-Munguía, José Vázquez-Prado, Lorenza González-Mariscal
Silencing Zonula occludens 2 (ZO-2), a tight junctions (TJ) scaffold protein, in epithelial cells (MDCK ZO-2 KD) triggers: 1) Decreased cell to substratum attachment, accompanied by reduced expression of claudin-7 and integrin β1, and increased vinculin recruitment to focal adhesions and stress fibers formation; 2) Lowered cell-cell aggregation and appearance of wider intercellular spaces; 3) Increased RhoA/ROCK activity, mediated by GEF-HI recruitment to cell borders by cingulin; 4) Increased Cdc42 activity, mitotic spindle disorientation and the appearance of cysts with multiple lumens; 5) Increased Rac and cofilin activity, multiple lamellipodia formation and random cell migration but increased wound closure; 6) Diminished cingulin phosphorylation and disappearance of planar network of microtubules at the TJ region; and 7) Increased transepithelial electrical resistance at steady state, coupled to an increased expression of ZO-1 and claudin-4 and a decreased expression of claudin-2 and paracingulin...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#14
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537922/cooperative-but-distinct-early-co-signaling-events-originate-from-erbb2-and-erbb1-receptors-upon-trastuzumab-treatment-in-breast-cancer-cells
#15
Paola Bagnato, Alessia Castagnino, Katia Cortese, Maria Bono, Silvia Grasso, Grazia Bellese, Tiziana Daniele, Richard Lundmark, Paola Defilippi, Patrizio Castagnola, Carlo Tacchetti
ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536952/ncam-affects-directional-lamellipodia-formation-of-bmscs-via-%C3%AE-1-integrin-signal-mediated-cofilin-activity
#16
Jia-Jia Bi, Jing Li, Bin-Feng Cheng, Hai-Jie Yang, Qiong-Qiong Ding, Rui-Fei Wang, Su-Juan Chen, Zhi-Wei Feng
The neural cell adhesion molecule (NCAM), a key member of the immunoglobulin-like CAM family, was reported to regulate the migration of bone marrow-derived mesenchymal stem cells (BMSCs). However, the detailed cellular behaviors including lamellipodia formation in the initial step of directional migration remain largely unknown. In the present study, we reported that NCAM affects the lamellipodia formation of BMSCs. Using BMSCs from Ncam knockout mice we found that Ncam deficiency significantly impaired the migration and the directional lamellipodia formation of BMSCs...
May 23, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28536263/axodendritic-sorting-and-pathological-missorting-of-tau-is-isoform-specific-and-determined-by-axon-initial-segment-architecture
#17
Hans Zempel, Frank Dennissen, Yatender Kumar, Julia Luedtke, Jacek Biernat, Eva-Maria Mandelkow, Eckhard Mandelkow
Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS but their physiological and pathological differences have long remained remain elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau-Diffusion-Barrier (TDB), located within the Axon-Initial-Segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28513458/cofilin-a-protein-controlling-dynamics-of-actin-filaments
#18
Zofia Ostrowska, Joanna Moraczewska
Cofilins are evolutionary conserved proteins present in all Eukaryotic cells. Their primary function is dynamic reorganization of actin cytoskeleton. Two cofilin isoforms are known: cofilin 1, present in all studied non-muscle cells and in embryonic muscle cells, and cofilin 2, which dominates in mature skeletal and cardiac muscles. Polypeptide chains of both isoforms fold into a structure homological to a conservative ADF (actin depolymerizing factor) domain, which is characteristic of actin depolymerizing factor...
May 5, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28502459/discovery-of-indolin-2-one-derivatives-as-potent-pak4-inhibitors-structure-activity-relationship-analysis-biological-evaluation-and-molecular-docking-study
#19
Jing Guo, Mingyue Zhu, Tianxiao Wu, Chenzhou Hao, Kai Wang, Zizheng Yan, Wanxu Huang, Jian Wang, Dongmei Zhao, Maosheng Cheng
Utilizing a pharmacophore hybridization approach, a novel series of substituted indolin-2-one derivatives were designed, synthesized and evaluated for their in vitro biological activities against p21-activated kinase 4. Compounds 11b, 12d and 12g exhibited the most potent inhibitory activity against PAK4 (IC50=22nM, 16nM and 27nM, respectively). Among them, compound 12g showed the highest antiproliferative activity against A549 cells (IC50=0.83μM). Apoptosis analysis in A549 cells suggested that compound 12g delayed cell cycle progression by arresting cells in the G2/M phase of the cell cycle, retarding cell growth...
July 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28502289/the-chronophin-activation-is-necessary-in-doxorubicin-induced-actin-cytoskeleton-alteration
#20
Su Jin Lee, Jeen Woo Park, Beom Sik Kang, Dong-Seok Lee, Hyun-Shik Lee, Sooyoung Choi, Oh-Shin Kwon
Although it is known that doxorubicin (Dox)-induced oxidative stress is associated with its cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations resulting in central stress fiber disruption at early time points and later cortical actin formation at the cell periphery in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling...
May 15, 2017: BMB Reports
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