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Cellular Signaling (cellular + signaling)
Terms modified by Cellular Signaling Selected AbstractsThree-dimensional slice cultures from murine fetal gut for investigations of the enteric nervous systemDEVELOPMENTAL DYNAMICS, Issue 1 2007Marco Metzger Abstract Three-dimensional intestinal cultures offer new possibilities for the examination of growth potential, analysis of time specific gene expression, and spatial cellular arrangement of enteric nervous system in an organotypical environment. We present an easy to produce in vitro model of the enteric nervous system for analysis and manipulation of cellular differentiation processes. Slice cultures of murine fetal colon were cultured on membrane inserts for up to 2 weeks without loss of autonomous contractility. After slice preparation, cultured tissue reorganized within the first days in vitro. Afterward, the culture possessed more than 35 cell layers, including high prismatic epithelial cells, smooth muscle cells, glial cells, and neurons analyzed by immunohistochemistry. The contraction frequency of intestinal slice culture could be modulated by the neurotransmitter serotonin and the sodium channel blocker tetrodotoxin. Coculture experiments with cultured neurospheres isolated from enhanced green fluorescent protein (eGFP) transgenic mice demonstrated that differentiating eGFP-positive neurons were integrated into the intestinal tissue culture. This slice culture model of enteric nervous system proved to be useful for studying cell,cell interactions, cellular signaling, and cell differentiation processes in a three-dimensional cell arrangement. Developmental Dynamics 236:128,133, 2007. © 2006 Wiley-Liss, Inc. [source] Fused protein of ,PKC activation loop and PDK1-interacting fragment (,AL-PIF) functions as a pseudosubstrate and an inhibitory molecule for PDK1 when expressed in cellsGENES TO CELLS, Issue 9 2006Takahiro Seki To elucidate the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in cellular signaling, we constructed and expressed a pseudosubstrate of PDK1, designated as ,AL-PIF, and characterized its properties in cultured cells. ,AL-PIF consists of two fused proteins of the protein kinase C, (,PKC) activation loop (,AL) and PDK1-interacting fragment (PIF). The phosphorylation of ,AL-PIF was detected with anti-,PKC phospho-Thr505 -specific antibody and was increased in proportion to the expression level of co-expressed GST-PDK1, indicating that it acts as a pseudosubstrate of PDK1. In cells expressing ,AL-PIF, basal phosphorylation level at the activation loop of PKB,, ,PKC and ,PKC was reduced, compared with that in control cells, suggesting that ,AL-PIF functions as an inhibitory molecule for PDK1. ,AL-PIF affected the stability, translocation and endogenous activity of PKCs. These effects of ,AL-PIF on ,PKC properties were confirmed by investigation using conditioned PDK1 knockout cells. Furthermore, apoptosis frequently occurred in cells expressing ,AL-PIF for 3 days. These findings revealed that ,AL-PIF served as an effective pseudosubstrate and an inhibitory molecule for PDK1, suggesting that this molecule can be used as a tool for investigating PDK-mediated cellular functions as well as being applicable for anti-cancer therapy. [source] The Complex Nature of Protein PhosphatasesIUBMB LIFE, Issue 6 2002Alistair T. R. Sim Abstract Protein phosphatases are integrally associated with the regulation of cellular signaling. The mechanisms underlying the specific regulatory roles are likely to be unique to each cell system. Nevertheless, analysis of phosphatase regulation in a number of systems has identified phosphatase targeting through association with a wide range of binding partners to be a fundamental mechanism of regulation. Using protein phosphatase 2A (PP2A) as an example, this snapshot summarizes these fundamental mechanisms of protein phosphatase regulation. [source] Neural differentiation of human embryonic stem cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2008Sujoy K. Dhara Abstract Availability of human embryonic stem cells (hESC) has enhanced human neural differentiation research. The derivation of neural progenitor (NP) cells from hESC facilitates the interrogation of human embryonic development through the generation of neuronal subtypes and supporting glial cells. These cells will likely lead to novel drug screening and cell therapy uses. This review will discuss the current status of derivation, maintenance and further differentiation of NP cells with special emphasis on the cellular signaling involved in these processes. The derivation process affects the yield and homogeneity of the NP cells. Then when exposed to the correct environmental signaling cues, NP cells can follow a unique and robust temporal cell differentiation process forming numerous phenotypes. J. Cell. Biochem. 105: 633,640, 2008. © 2008 Wiley-Liss, Inc. [source] Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1BMEDICINAL RESEARCH REVIEWS, Issue 4 2007Seokjoon Lee Abstract Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play essential roles in intracellular signal transduction by regulating the cellular level of tyrosine phosphorylation to control cell growth and differentiation, metabolism, cell migration, gene transcription, ion-channel activity, immune response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many human diseases, including cancer, diabetes, and obesity. Therefore, small molecular inhibitors of PTP1B can be promising drug candidates. Because of the structural homologies in many families of PTPs, it is a challenging task to find inhibitors specific to each PTP. Recent studies suggested that secondary binding pockets or peripheral binding sites around the conserved active site should be exploited to design novel potent and selective PTP1B inhibitors. In this review, we discuss the structural and biological features of small molecular PTP1B-specific inhibitors, with particular emphasis on small molecular inhibitors targeting PTP1B over the other PTPs that have been synthesized in the past 4 years. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 553,573, 2007 [source] Resveratrol: Preventing properties against vascular alterations and ageingMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2005Dominique Delmas Abstract Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases. [source] Regulation of insulin action by an extract of Artemisia dracunculus L. in primary human skeletal muscle culture: A proteomics approach,PHYTOTHERAPY RESEARCH, Issue 9 2010Indu Kheterpal Abstract An ethanolic extract of Artemisia dracunculus L. (PMI 5011) has been observed to decrease glucose and insulin levels in animal models and enhance cellular signaling in cultured cells. To determine the mechanism of action of PMI-5011, we have measured changes in protein expression in human primary skeletal muscle culture (HSMC) from subjects with Type 2 diabetes. After obtaining skeletal muscle biopsies, HSMCs were initiated, grown to confluence, and exposed to 10,µg/mL PMI 5011 overnight. Two-dimensional difference in-gel electrophoresis was used to separate proteins, and liquid chromatography mass spectrometry was used to identify differentially regulated proteins. Additionally, real-time polymerase chain reaction (PCR) was used to confirm candidate proteins identified. These data demonstrate that a well characterized botanical extract of Artemisia dracunculus L. significantly modulates proteins involved in regulating inflammatory pathways, particularly the NF,B complex system. Copyright © 2010 John Wiley & Sons, Ltd. [source] On the structural diversity of Shiga toxin glycosphingolipid receptors in lymphoid and myeloid cells determined by nanoelectrospray ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 15 2010Petra Hoffmann Shiga toxin (Stx, synonymous to verotoxin, VT) binds with high and low affinity to the globo-series neutral glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer or Gal,4Gal,4Glc,1Cer, also known as CD77) and globotetraosylceramide (Gb4Cer or GalNAc,3Gal,4Gal,4Glc,1Cer), respectively, which represent the targets of Stxs on many different cell types. B-cell-derived Raji cells and THP-1 cells of monocytic origin are widely used for the investigation of Stx-mediated cellular response, because Stx is known to cause cell death in both cell lines. Despite their functional importance, the Stx receptors of Raji and THP-1 cells have so far not been investigated. This prompted us to explore the structures of their GSL receptors in detail by means of nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI-QTOF-MS) with collision-induced dissociation (CID) in conjunction with Stx1 as well as anti-Gb3Cer and anti-Gb4Cer antibodies. Using the combination of a thin-layer chromatography (TLC) overlay assay and MS1 and MS2 analysis we identified Gb3Cer (d18:1, C24:1/C24:0) as the prevalent Stx1-receptor accompanied by less abundant Gb3Cer (d18:1, C16:0) in the neutral GSL fraction of Raji cells. The same Gb3Cer species but with almost equal proportions of the C24:1/C24:0 and C16:0 variants were found in THP-1 cells. In addition, unusual hydroxylated Gb3Cer (d18:1, C24:1/C24:0) and Gb3Cer (d18:1, C26:1) could be identified in trace quantities in both cell lines. As the most obvious difference between Raji and THP-1 cells we observed the expression of Gb4Cer in THP-1 cells, whereas Raji cells failed to express this elongation product of Gb3Cer. Both short- and long-chain fatty acid carrying Gb4Cer (d18:1, C16:0) and Gb4Cer (d18:1, C24:1/C24:0), respectively, were the prevalent Gb4Cer variants. This first report on the differential expression of Gb3Cer and Gb4Cer and their structural diversity in lymphoid and myeloid cell lines supports the hypothesis that such heterogeneities might play a functional role in the molecular assembly of GSLs in membrane organization and cellular signaling of Stx-susceptible cells. Copyright © 2010 John Wiley & Sons, Ltd. [source] Expression of ezrin, Bcl-2, and Ki-67 in chondrosarcomasAPMIS, Issue 10 2010MIRVA SÖDERSTRÖM Söderström M, Palokangas T, Vahlberg T, Böhling T, Aro H, Carpen O. Expression of ezrin, Bcl-2, and Ki-67 in chondrosarcomas. APMIS 2010; 118: 769,76. The aim of the present study was to investigate whether the expression of ezrin, a membrane-cytoskeleton linker and regulator of cellular signaling, is associated with clinical features of chondrosarcoma. For this purpose, we studied the expression of ezrin in 54 chondrosarcomas by immunohistochemistry and correlated the expression with other tumor characteristics, markers of proliferation, apoptosis and with clinical parameters. The intensity of ezrin staining increased with the histologic grade, and a significant positive association existed between the tumor grade and ezrin expression (p = 0.0475). In addition, there was a positive correlation between the expression of ezrin and Bcl-2, an anti-apoptotic protein (r = 0.83, p < 0.0001), as well as between ezrin expression and increased proliferation as measured by Ki-67 index (r = 0.70, p < 0.0001). The positive correlation of ezrin expression with Bcl-2 and Ki-67 as well as with tumor grade suggests that an aggressive behavior of chondrosarcoma may be related to activation of ezrin and that ezrin inhibitors could provide a much needed adjuvant therapy in chondrosarcomas. In conclusion, our results indicate that high ezrin expression correlates with aggressive features of chondrosarcomas. Further analyses on the pathways downstream of ezrin are warranted. [source] Role of mitochondrial ion channels in cell deathBIOFACTORS, Issue 4 2010Shin-Young Ryu Abstract Ion channels located in the outer and inner mitochondrial membranes are key regulators of cellular signaling for life and death. Permeabilization of mitochondrial membranes is one of the most critical steps in the progression of several cell death pathways. The mitochondrial apoptosis-induced channel (MAC) and the mitochondrial permeability transition pore (mPTP) play major roles in these processes. Here, the most recent progress and current perspectives about the roles of MAC and mPTP in mitochondrial membrane permeabilization during cell death are presented. The crosstalk signaling of MAC and mPTP formation/activation mediated by cytosolic Ca2+ signaling, Bcl-2 family proteins, and other mitochondrial ion channels is also discussed. Understanding the mechanisms that regulate opening and closing of MAC and mPTP has revealed new therapeutic targets that potentially could control cell death in pathologies such as cancer, ischemia/reperfusion injuries, and neurodegenerative diseases. [source] Gene expression in arcuate nucleus-median eminence of rats treated with leptin or ciliary neurotrophic factorBIOFACTORS, Issue 2 2007Suresh Ambati Abstract Ciliary neurotrophic factor (CNTF) and leptin are cytokine-like hormones and act on their corresponding receptors in the hypothalamic arcuate nucleus (ARC). The present study was designed to assess effects of intracerebroventricular (ICV) injection of leptin and CNTF on gene expression in micropunched hypothalamic arcuate nucleus-median eminence (ARCME) complex samples from rats. Male Sprague Dawley rats were implanted with lateral cerebroventricular cannulas for administration of control, 10 ,g/d leptin or 5 ,g/d CNTF for four days. Real-time Taqman RT-PCR was used to quantitatively compare the mRNA levels of selected genes in the ARC-ME complex. Leptin and CNTF increased ARC-ME mRNA levels of signal transducer and activator of transcription 3 (STAT3) by 64.5 and 124.7% (p < 0.01), suppressor of cytokine signaling 3 (SOCS3) by 258.9 and 1063.9% (p < 0.01), cocaine and amphetamine regulated transcript (CART) by 102.7 and 123.1% (p < 0.01), and proopiomelanocortin (POMC2) by 374.1 and 264.9% (p < 0.01), respectively. Leptin increased growth hormone releasing hormone (GHRH) by 309.9% (p < 0.01), while CNTF increased janus kinase 2 (JAK2) mRNA by 31.7% (p < 0.01) and decreased gonadotropin releasing hormone 1 (GNRH1) by 59.7% (p < 0.01), mitogen activated protein kinase 1 (MAPK1) by 19.4% (p < 0.05) and tyrosine hydroxylase (TH) by 74.5% (p < 0.05). Significant reduction in daily food intake and body weights by both the treatments was observed. Also, decrease in weights of fat pads was concomitant with lowered serum insulin and leptin levels. Our findings show that leptin and CNTF engage both convergent and divergent pathways involved in feeding, cellular signaling, inflammation, and other related regulatory systems. [source] ,-Herpesviruses and cellular signaling in AIDS-associated malignanciesCANCER SCIENCE, Issue 9 2007Kohji Noguchi ,-Herpesviruses, Epstein,Barr virus (EBV/HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), are involved in human carcinogenesis, particularly in immunocompromised patients. Virus-associated malignancies are becoming of significant concern for the mortality of long-lived immunocompromised patients, and therefore, research of advanced strategies for AIDS-related malignancies is an important field in cancer chemotherapy. Detailed understanding of the EBV and KSHV lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy. The present review gives a simple outline of the functional interactions between KSHV- and EBV-viral gene products and host cell deregulated signaling pathways as possible targets of chemotherapy against AIDS-related malignancies. (Cancer Sci 2007; 98: 1288,1296) [source] Signal Transducers and Activators of Transcription as Targets for Small Organic MoleculesCHEMBIOCHEM, Issue 13 2008Thorsten Berg Dr. Abstract Signal transducers and activators of transcription (STATs) are a family of transcription factors that are of central importance for cellular signaling and have therefore emerged as attractive target proteins for cell-permeable small molecules. This review outlines the basic concept of STAT signaling, the relevance of individual members of the STAT family for cellular signaling and human disease, and generally applicable approaches taken to the identification of small-molecule inhibitors of STATs. [source] | ||||||||||||||||