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GPC3 reduces cell proliferation in renal carcinoma cell lines

Valsechi, Marina Curado; Oliveira, Ana Beatriz Bortolozo; Conceição, André Luis Giacometti; Stuqui, Bruna; Candido, Natalia Maria; Provazzi, Jocelan Scarin; Araujo, Luiza Ferreira de; Silva Junior, Wilson Araújo da; Calmon, Marilia de Freitas; Rahal,
Fonte: BMC Publicador: BMC
Tipo: Artigo de Revista Científica
EN
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Abstract Background Glypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma. Methods Five clear cell renal cell carcinoma cell lines and carcinoma samples were used to analyze GPC3 mRNA expression (qRT-PCR). Then, representative cell lines, one primary renal carcinoma (786-O) and one metastatic renal carcinoma (ACHN), were chosen to carry out functional studies. We constructed a GPC3 expression vector and transfected the renal carcinoma cell lines, 786-O and ACHN. GPC3 overexpression was analyzed using qRT-PCR and immunocytochemistry. We evaluated cell proliferation using MTT and colony formation assays. Flow cytometry was used to evaluate apoptosis and perform cell cycle analyses. Results We observed that GPC3 is downregulated in clear cell renal cell carcinoma samples and cell lines compared with normal renal samples. GPC3 mRNA expression and protein levels in 786-O and ACHN cell lines increased after transfection with the GPC3 expression construct...

GPC3 reduces cell proliferation in renal carcinoma cell lines

Valsechi, Marina Curado; Bortolozo Oliveira, Ana Beatriz; Giacometti Conceicao, Andre Luis; Stuqui, Bruna; Candido, Natalia Maria; Scarin Provazzi, Paola Jocelan; Araujo, Luiza Ferreira de; Silva, Wilson Araujo; Calmon, Marilia de Freitas; Rahal, Paula
Fonte: Biomed Central Ltd Publicador: Biomed Central Ltd
Tipo: Artigo de Revista Científica Formato: 11
ENG
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Background: Glypican 3 (GPC3) is a member of the family of glypican heparan sulfate proteoglycans (HSPGs). The GPC3 gene may play a role in controlling cell migration, negatively regulating cell growth and inducing apoptosis. GPC3 is downregulated in several cancers, which can result in uncontrolled cell growth and can also contribute to the malignant phenotype of some tumors. The purpose of this study was to analyze the mechanism of action of the GPC3 gene in clear cell renal cell carcinoma.Methods: Five clear cell renal cell carcinoma cell lines and carcinoma samples were used to analyze GPC3 mRNA expression (qRT-PCR). Then, representative cell lines, one primary renal carcinoma (786-O) and one metastatic renal carcinoma (ACHN), were chosen to carry out functional studies. We constructed a GPC3 expression vector and transfected the renal carcinoma cell lines, 786-O and ACHN. GPC3 overexpression was analyzed using qRT-PCR and immunocytochemistry. We evaluated cell proliferation using MTT and colony formation assays. Flow cytometry was used to evaluate apoptosis and perform cell cycle analyses.Results: We observed that GPC3 is downregulated in clear cell renal cell carcinoma samples and cell lines compared with normal renal samples. GPC3 mRNA expression and protein levels in 786-O and ACHN cell lines increased after transfection with the GPC3 expression construct...

Cytochrome c release and mitochondria involvement in programmed cell death induced by acetic acid in Saccharomyces cerevisiae

Ludovico, Paula; Rodrigues, Fernando José dos Santos; Almeida, A. J.; Silva, Manuel T.; Barrientos, Antoni; Côrte-Real, Manuela
Fonte: American Society for Cell Biology. Publicador: American Society for Cell Biology.
Tipo: Artigo de Revista Científica
Publicado em /08/2002 ENG
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Evidence is presented that mitochondria are implicated in the previously described programmed cell death (PCD) process induced by acetic acid in Saccharomyces cerevisiae. In yeast cells undergoing a PCD process induced by acetic acid, translocation of cytochrome c (CytC) to the cytosol and reactive oxygen species production, two events known to be proapoptotic in mammals, were observed. Associated with these events, reduction in oxygen consumption and in mitochondrial membrane potential was found. Enzymatic assays showed that the activity of complex bc1 was normal, whereas that of cytochrome c oxidase (COX) was strongly decreased. This decrease is in accordance with the observed reduction in the amounts of COX II subunit and of cytochromes a+a3. The acetic acid-induced PCD process was found to be independent of oxidative phosphorylation because it was not inhibited by oligomycin treatment. The inability of S. cerevisiae mutant strains (lacking mitochondrial DNA, heme lyase, or ATPase) to undergo acetic acid-induced PCD and in the ATPase mutant (knockout in ATP10) the absence of CytC release provides further evidence that the process is mediated by a mitochondria-dependent apoptotic pathway. The understanding of the involvement of a mitochondria-dependent apoptotic pathway in S. cerevisiae PCD process will be most useful in the further elucidation of an ancestral pathway common to PCD in metazoans.; Fundação para a Ciência e a Tecnologia (FCT) - PRAXIS XXI.; Muscular Dystrophy Association – grant MDACU01991001.

Microtubule Disruption in Keratinocytes Induces Cell-Cell Adhesion through Activation of Endogenous E-Cadherin

Kee, Sun-Ho; Steinert, Peter M.
Fonte: The American Society for Cell Biology Publicador: The American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em /07/2001 EN
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The association of the cytoskeleton with the cadherin–catenin complex is essential for strong cell-cell adhesion in epithelial cells. In this study, we have investigated the effect of microtubule organization on cell-cell adhesion in differentiating keratinocytes. When microtubules of normal human epidermal keratinocytes (NHEKs) grown in low calcium media (0.05 mM) were disrupted with nocodazole or colcemid, cell-cell adhesion was induced through relocalization of the E-cadherin–catenin–actin complex to the cell periphery. This was accompanied by actin polymerization. Also, it was found that microtubule disruption-induced cell-cell adhesion was significantly reduced in more advanced differentiated keratinocytes. For example, when NHEK cells cultured under high calcium (1.2 mM) for 8 d and then in low calcium for 1 d were treated with nocodazole, there was no induction of cell-cell adhesion. Also long-term treatment of a phorbol ester for 48 h inhibited nocodazole-induced cell-cell adhesion of NHEK. Furthermore, this nocodazole-induced cell-cell adhesion could be observed in squamous cancer cell lines (A431 and SCC-5, -9, and -25) under low calcium condition, but not in the keratinocyte cell lines derived from normal epidermis (HaCaT...

Involvement of IQGAP1, an Effector of Rac1 and Cdc42 GTPases, in Cell-Cell Dissociation during Cell Scattering

Fukata, Masaki; Nakagawa, Masato; Itoh, Naohiro; Kawajiri, Aie; Yamaga, Masaki; Kuroda, Shinya; Kaibuchi, Kozo
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2001 EN
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We have previously proposed that IQGAP1, an effector of Rac1 and Cdc42, negatively regulates cadherin-mediated cell-cell adhesion by interacting with β-catenin and by causing the dissociation of α-catenin from cadherin–β-catenin–α-catenin complexes and that activated Rac1 and Cdc42 positively regulate cadherin-mediated cell-cell adhesion by inhibiting the interaction of IQGAP1 with β-catenin. However, it remains to be clarified in which physiological processes the Rac1-Cdc42-IQGAP1 system is involved. We here examined whether the Rac1-IQGAP1 system is involved in the cell-cell dissociation of Madin-Darby canine kidney II cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hepatocyte growth factor (HGF)-induced cell scattering. By using enhanced green fluorescent protein (EGFP)-tagged α-catenin, we found that EGFP–α-catenin decreased prior to cell-cell dissociation during cell scattering. We also found that the Rac1-GTP level decreased after stimulation with TPA and that the Rac1-IQGAP1 complexes decreased, while the IQGAP1–β-catenin complexes increased during action of TPA. Constitutively active Rac1 and IQGAP1 carboxyl terminus, a putative dominant-negative mutant of IQGAP1, inhibited the disappearance of α-catenin from sites of cell-cell contact induced by TPA. Taken together...

Herpes Simplex Virus gE/gI Expressed in Epithelial Cells Interferes with Cell-to-Cell Spread

Collins, Wendy J.; Johnson, David C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2003 EN
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35.77%
The herpes simplex virus (HSV) glycoprotein heterodimer gE/gI plays an important role in virus cell-to-cell spread in epithelial and neuronal tissues. In an analogous fashion, gE/gI promotes virus spread between certain cell types in culture, e.g., keratinocytes and epithelial cells, cells that are polarized or that form extensive cell junctions. One mechanism by which gE/gI facilitates cell-to-cell spread involves selective sorting of nascent virions to cell junctions, a process that requires the cytoplasmic domain of gE. However, the large extracellular domains of gE/gI also appear to be involved in cell-to-cell spread. Here, we show that coexpression of a truncated form of gE and gI in a human keratinocyte line, HaCaT cells, decreased the spread of HSV between cells. This truncated gE/gI was found extensively at cell junctions. Expression of wild-type gE/gI that accumulates at intracellular sites, in the trans-Golgi network, did not reduce cell-to-cell spread. There was no obvious reduction in production of infectious HSV in cells expressing gE/gI, and virus particles accumulated at cell junctions, not at intracellular sites. Expression of HSV gD, which is known to bind virus receptors, also blocked cell-to-cell spread. Therefore...

MAGI-1 Is Required for Rap1 Activation upon Cell-Cell Contact and for Enhancement of Vascular Endothelial Cadherin-mediated Cell AdhesionD⃞V⃞

Sakurai, Atsuko; Fukuhara, Shigetomo; Yamagishi, Akiko; Sako, Keisuke; Kamioka, Yuji; Masuda, Michitaka; Nakaoka, Yoshikazu; Mochizuki, Naoki
Fonte: The American Society for Cell Biology Publicador: The American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em /02/2006 EN
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Rap1 is a small GTPase that regulates adherens junction maturation. It remains elusive how Rap1 is activated upon cell-cell contact. We demonstrate for the first time that Rap1 is activated upon homophilic engagement of vascular endothelial cadherin (VE-cadherin) at the cell-cell contacts in living cells and that MAGI-1 is required for VE-cadherin-dependent Rap1 activation. We found that MAGI-1 localized to cell-cell contacts presumably by associating with β-catenin and that MAGI-1 bound to a guanine nucleotide exchange factor for Rap1, PDZ-GEF1. Depletion of MAGI-1 suppressed the cell-cell contact-induced Rap1 activation and the VE-cadherin-mediated cell-cell adhesion after Ca2+ switch. In addition, relocation of vinculin from cell-extracellular matrix contacts to cell-cell contacts after the Ca2+ switch was inhibited in MAGI-1-depleted cells. Furthermore, inactivation of Rap1 by overexpression of Rap1GAPII impaired the VE-cadherin-dependent cell adhesion. Collectively, MAGI-1 is important for VE-cadherin-dependent Rap1 activation upon cell-cell contact. In addition, once activated, Rap1 upon cell-cell contacts positively regulate the adherens junction formation by relocating vinculin that supports VE-cadherin-based cell adhesion.

Herpes Simplex Virus gE/gI Must Accumulate in the trans-Golgi Network at Early Times and Then Redistribute to Cell Junctions To Promote Cell-Cell Spread

Farnsworth, Aaron; Johnson, David C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2006 EN
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35.77%
Herpes simplex virus (HSV) glycoprotein heterodimer gE/gI is necessary for virus spread in epithelial and neuronal tissues. Deletion of the relatively large gE cytoplasmic (CT) domain abrogates the ability of gE/gI to mediate HSV spread. The gE CT domain is required for the sorting of gE/gI to the trans-Golgi network (TGN) in early stages of virus infection, and there are several recognizable TGN sorting motifs grouped near the center of this domain. Late in HSV infection, gE/gI, other viral glycoproteins, and enveloped virions redistribute from the TGN to epithelial cell junctions, and the gE CT domain is also required for this process. Without the gE CT domain, newly enveloped virions are directed to apical surfaces instead of to cell junctions. We hypothesized that the gE CT domain promotes virus envelopment into TGN subdomains from which nascent enveloped virions are sorted to cell junctions, a process that enhances cell-to-cell spread. To characterize elements of the gE CT domain involved in intracellular trafficking and cell-to-cell spread, we constructed a panel of truncation mutants. Specifically, these mutants were used to address whether sorting to the TGN and redistribution to cell junctions are necessary, and sufficient...

Cell-Cell Spread of Human Immunodeficiency Virus Type 1 Overcomes Tetherin/BST-2-Mediated Restriction in T cells▿

Jolly, Clare; Booth, Nicola J.; Neil, Stuart J. D.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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35.77%
Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4+ T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together...

Determining the Involvement and Therapeutic Implications of Host Cellular Factors in Hepatitis C Virus Cell-to-Cell Spread

Barretto, Naina; Sainz, Bruno; Hussain, Snawar; Uprichard, Susan L.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /05/2014 EN
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Hepatitis C virus (HCV) infects 180 million people worldwide and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. It has been shown that HCV can spread to naive cells using two distinct entry mechanisms, “cell-free” entry of infectious extracellular virions that have been released by infected cells and direct “cell-to-cell” transmission. Here, we examined host cell requirements for HCV spread and found that the cholesterol uptake receptor NPC1L1, which we recently identified as being an antiviral target involved in HCV cell-free entry/spread, is also required for the cell-to-cell spread. In contrast, the very low density lipoprotein (VLDL) pathway, which is required for the secretion of cell-free infectious virus and thus has been identified as an antiviral target for blocking cell-free virus secretion/spread, is not required for cell-to-cell spread. Noting that HCV cell-free and cell-to-cell spread share some common factors but not others, we tested the therapeutic implications of these observations and demonstrate that inhibitors that target cell factors required for both forms of HCV spread exhibit synergy when used in combination with interferon (a representative inhibitor of intracellular HCV production)...

Mechanical Regulation of Epithelial Cell Collective Migration

Ng, Mei Rosa
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation
EN_US
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Cell migration is a fundamental biological process involved in tissue development, wound repair, and diseases such as cancer metastasis. It is a biomechanical process involving the adhesion of a cell to a substratum, usually an elastic extracellular matrix, as well as the physical contraction of the cell driven by intracellular actomyosin network. In the migration of cells as a group, known as collective migration, the cells are also physically linked to one another through cell-cell adhesions. How mechanical interactions with cell substratum and with neighboring cells regulate movements during collective migration, nevertheless, is poorly understood. To address this question, the effects of substrate stiffness on sheet migration of MCF10A epithelial cells were systematically analyzed. Speed, persistence, directionality and coordination of individual cells within the migrating sheet were all found to increase with substrate stiffening. Substrate stiffening also enhanced the propagation of coordinated movement from the sheet edge into the monolayer, which correlated with an upregulation of myosin-II activity in sheet edge cells. This mechano-response was dependent on cadherin-mediated cell-cell adhesions, which are required for the transmission of directional cue. Importantly...

A conserved cell growth cycle can account for the environmental stress responses of divergent eukaryotes

Slavov, Nikolai; Airoldi, Edoardo Maria; van Oudenaarden, A.; Botstein, D.
Fonte: American Society for Cell Biology (ASCB) Publicador: American Society for Cell Biology (ASCB)
Tipo: Artigo de Revista Científica
EN_US
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45.69%
The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene-expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism, transitions from the HOC phase to the LOC phase, can account for much of the common environmental stress response (ESR) and for the cross protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat-stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in human can explain gene-expression and respiratory patterns observed in these organisms. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast...

Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in esophageal squamous cell carcinoma

Paccez, Juliano D.; Duncan, Kristal; Vava, Akhona; Correa, Ricardo G.; Libermann, Towia A.; Parker, M. Iqbal; Zerbini, Luiz F.
Fonte: The American Society for Cell Biology Publicador: The American Society for Cell Biology
Tipo: Artigo de Revista Científica
EN_US
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The receptor tyrosine kinase Axl has been described as an oncogene, and its deregulation has been implicated in the progression of several human cancers. While the role of Axl in esophageal adenocarcinoma has been addressed, there is no information about its role in esophageal squamous cell carcinoma (OSCC). In the current report, we identified, for the first time, deregulation of Axl expression in OSCC. Axl is consistently overexpressed in OSCC cell lines and human tumor samples, mainly in advanced stages of the disease. Blockage of Axl gene expression by small interfering RNA inhibits cell survival, proliferation, migration, and invasion in vitro and esophageal tumor growth in vivo. Additionally, repression of Axl expression results in Akt-dependent inhibition of pivotal genes involved in the nuclear factor-kappaB (NF-κB) pathway and in the induction of glycogen synthase kinase 3β (GSK3β) activity, resulting in loss of mesenchymal markers and induction of epithelial markers. Furthermore, treatment of esophageal cancer cells with the Akt inhibitor wortmannin inhibits NF-κB signaling, induces GSK3β activity, and blocks OSCC cell proliferation in an Axl-dependent manner. Taken together, our results establish a clear role for Axl in OSCC tumorigenesis with potential therapeutic implications.

Theoretical analysis of epigenetic cell memory by nucleosome modification

Dodd, I.; Micheelsen, M.; Sneppen, K.; Thon, G.
Fonte: Cell Press Publicador: Cell Press
Tipo: Artigo de Revista Científica
Publicado em //2007 EN
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45.62%
Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Such epigenetic control is often associated with alternative covalent modifications of histones. The stability and heritability of the states are thought to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes. We developed a simplified stochastic model for dynamic nucleosome modification based on the silent mating-type region of the yeast Schizosaccharomyces pombe. We show that the mechanism can give strong bistability that is resistant both to high noise due to random gain or loss of nucleosome modifications and to random partitioning upon DNA replication. However, robust bistability required: (1) cooperativity, the activity of more than one modified nucleosome, in the modification reactions and (2) that nucleosomes occasionally stimulate modification beyond their neighbor nucleosomes, arguing against a simple continuous spreading of nucleosome modification.; http://www.cell.com/; Ian B. Dodd, Mille A. Micheelsen, Kim Sneppen and Geneviève Thon

USP9X Enhances the Polarity and Self-Renewal of Embryonic Stem Cell-derived Neural Progenitors

Jolly, L.; Taylor, V.; Wood, S.
Fonte: Amer Soc Cell Biology Publicador: Amer Soc Cell Biology
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
45.71%
The substrate-specific deubiquitylating enzyme USP9X is a putative “stemness” gene expressed in many progenitor cell populations. To test its function in embryonic stem cell-derived neural progenitor/stem cells, we expressed USP9X from a Nestin promoter. Elevated USP9X levels resulted in two phenomena. First, it produced a dramatically altered cellular architecture wherein the majority (>80%) of neural progenitors was arranged into radial clusters. These progenitors expressed markers of radial glial cells and were highly polarized with adherens junction proteins (N-cadherin, -catenin, and AF-6) and apical markers (Prominin1, atypical protein kinase C-) as well as Notch, Numb, and USP9X itself, concentrated at the center. The cluster centers were also devoid of nuclei and so resembled the apical end-feet of radial progenitors in the neural tube. Second, USP9X overexpression caused a fivefold increase in the number of radial progenitors and neurons, in the absence of exogenous growth factors. 5-Bromo-2-deoxyuridine labeling, as well as the examination of the brain lipid-binding protein:III-tubulin ratio, indicated that nestin-USP9X enhanced the self-renewal of radial progenitors but did not block their subsequent differentiation to neurons and astrocytes. nestin-USP9X radial progenitors reformed clusters after passage as single cells...

αB-Crystallin inhibits the cell toxicity associated with amyloid fibril formation by κ-casein and the amyloid-β peptide; alphaB-Crystallin inhibits the cell toxicity associated with amyloid fibril formation by kappa-casein and the amyloid-beta peptide

Dehle, F.; Ecroyd, H.; Musgrave, I.; Carver, J.
Fonte: Cell Stress Soc International Publicador: Cell Stress Soc International
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
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45.71%
Amyloid fibril formation is associated with diseases such as Alzheimer's, Parkinson's, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also investigated whether fibril formation by amyloid-β1-40 (Aβ(1-40)), the peptide associated with Alzheimer's disease, was inhibited by αB-crystallin and if this affected the toxicity of Aβ. To this end, either RCMκ-CN or Aβ(1-40) was incubated at neutral pH to induce fibril formation before treating PC12 cells and assessing cell viability. Incubated (fibrillar) RCMκ-CN was more toxic to PC12 cells than native RCMκ-CN with the highest level of toxicity being associated with mature fibrils and protofibrils. Furthermore, the toxicity of RCMκ-CN was attenuated when its fibril formation was inhibited...

Cell division requires a direct link between microtubule-bound RacGAP and Anillin in the contractile ring

Gregory, Stephen L; Ebrahimi, Saman; Milverton, Joanne; Jones, Whitney M; Bejsovec, Amy; Saint, Robert
Fonte: Cell Press Publicador: Cell Press
Tipo: Artigo de Revista Científica
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The mitotic microtubule array plays two primary roles in cell division. It acts as a scaffold for the congression and separation of chromosomes, and it specifies and maintains the contractile-ring position. The current model for initiation of Drosophila a

Opposing Functions of the T Cell Receptor Kinase ZAP-70 in Immunity and Tolerance Differentially Titrate in Response to Nucleotide Substitutions

Siggs, Owen; Miosge, Lisa; Yates (previously Loy), Adele; Kucharska, Edyta; Sheahan, Daniel; Brdicka, Tomas; Weiss, Arthur; Liston, Adrian; Goodnow, Christopher
Fonte: Cell Press Publicador: Cell Press
Tipo: Artigo de Revista Científica
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45.62%
Null mutations that cripple T cell receptor (TCR) signaling explain rare primary immunodeficiencies, but it is not understood why more common polymorphisms that lead to subtle TCR signaling defects are paradoxically associated with autoimmunity. Here we a

Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner

Kolahgar, Golnar; Suijkerbuijk, Saskia J. E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia
Fonte: Cell/Elsevier Publicador: Cell/Elsevier
Tipo: Article; published version
EN
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This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.devcel.2015.06.010; Through their lifetime cells may suffer insults that reduce their fitness and disrupt their function and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem cell and tissue population dynamics. We show that healthy cells induce clonal extinction in weak tissues, targeting both stem and differentiated cells for elimination. We also find that competition induces stem cell proliferation and self-renewal in healthy tissue, promoting selective advantage and tissue colonization. Finally, we show that winner cell proliferation is fuelled by the JAK-STAT ligand Unpaired-3, produced by Minute-/+ cells in response to chronic JNK stress signaling.; This work was supported by a Cancer Research UK Programme Grant (E.P. and G.K. A12460), a Royal Society University Research fellowship to E.P. (UF090580)...

The Mitogen-Induced Increase in T Cell Size Involves PKC and NFAT Activation of Rel/NF-kB-Dependent c-myc Expression

Grumont, Raelene; Lock, Peter; Shannon, M Frances; Moore, Anna; Gerondakis, Steve; Mollinari, Michael
Fonte: Cell Press Publicador: Cell Press
Tipo: Artigo de Revista Científica
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45.7%
Cell growth during the G1 stage of the cell cycle is partly controlled by inducing c-myc expression, which in B cells is regulated by the NF-κB1 and c-Rel transcription factors. Here, we show that c-myc-dependent growth during T cell activation requires