oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Dynamic Network of Transcription and Pathway Crosstalk to Reveal Molecular Mechanism of MGd-Treated Human Lung Cancer Cells  [PDF]
Liyan Shao, Lishan Wang, Zhiyun Wei, Yuyu Xiong, Yang Wang, Kefu Tang, Yang Li, Guoyin Feng, Qinghe Xing, Lin He
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031984
Abstract: Recent research has revealed various molecular markers in lung cancer. However, the organizational principles underlying their genetic regulatory networks still await investigation. Here we performed Network Component Analysis (NCA) and Pathway Crosstalk Analysis (PCA) to construct a regulatory network in human lung cancer (A549) cells which were treated with 50 uM motexafin gadolinium (MGd), a metal cation-containing chemotherapeutic drug for 4, 12, and 24 hours. We identified a set of key TFs, known target genes for these TFs, and signaling pathways involved in regulatory networks. Our work showed that putative interactions between these TFs (such as ESR1/Sp1, E2F1/Sp1, c-MYC-ESR, Smad3/c-Myc, and NFKB1/RELA), between TFs and their target genes (such as BMP41/Est1, TSC2/Myc, APE1/Sp1/p53, RARA/HOXA1, and SP1/USF2), and between signaling pathways (such as PPAR signaling pathway and Adipocytokines signaling pathway). These results will provide insights into the regulatory mechanism of MGd-treated human lung cancer cells.
Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated endothelium promotes inflammation
My-Linh Ngo, Fakhri Mahdi, Dhaval Kolte, Zia Shariat-Madar
Journal of Inflammation , 2009, DOI: 10.1186/1476-9255-6-3
Abstract: The Prcp transcript expression in LPS-induced human umbilical vein endothelial cells (HUVEC) activation was determined by RT-PCR for mRNA. PRCP-dependent kallikrein pathway was determined either by Enzyme Linked ImmunoSorbent Assay (ELISA) or by biochemical assay.We report that PRCP is critical to the maintenance of the endothelial cells, and its upregulation contributes to the risk of developing inflammation. Significant elevation in kallikrein was seen on LPS-treated HUVECs. The conversion of PK to kallikrein was blocked by the inhibitor of PRCP, suggesting that PRCP might be a risk factor for inflammation.The increased PRCP lead to a sustained production of bradykinin in endothelium following LPS treatment. This amplification may be an additional mechanism whereby PRCP promotes a sustained inflammatory response. A better appreciation of the role of PRCP in endothelium may contribute to a better understanding of inflammatory vascular disorders and to the development of a novel treatment.Prolylcarboxypeptidase (PRCP) dysfunction is associated with adverse cardiovascular consequences such as inflammation and hypertension [1,2]. Although the physiological role(s) of PRCP is still poorly understood, PRCP has been shown to be an active participant in processes such as cell permeability via the activation of prekallikrein (PK) and the melanogenic signaling pathway [3]. PRCP-dependent plasma prekallikrein activation influences the permeability of the endothelium by liberating bradykinin (BK) from a protein precursor, high molecular weight kininogen (HK). BK- mediated bradykinin B 2 receptor activation leads to the release of nitric oxide and prostaglandins [4,5]. In addition, PRCP metabolizes angiotensin II (Ang II) to angiotensin 1–7 (Ang 1–7) and angiotensin III (Ang III) to angiotensin 2–7 (Ang 2–7). Ang 1–7 -mediated Ang 1–7 receptor Mas activation causes the release of prostaglandins and nitric oxide[6]. Thus, PRCP regulates Ang 1–7 – and BK – stimulated nitric oxid
Dynamic Analysis of Stochastic Transcription Cycles  [PDF]
Claire V. Harper,B?rbel Finkenst?dt,Dan J. Woodcock,S?nke Friedrichsen,Sabrina Semprini,Louise Ashall,David G. Spiller,John J. Mullins,David A. Rand,Julian R. E. Davis,Michael R. H. White
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000607
Abstract: In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly increased the cyclicity. Stochastically timed bursts of transcription in an apparently random subset of cells in a tissue may thus produce an overall coordinated but heterogeneous phenotype capable of acute responses to stimuli.
Dynamic Analysis of Stochastic Transcription Cycles  [PDF]
Claire V. Harper,B?rbel Finkenst?dt,Dan J. Woodcock,S?nke Friedrichsen,Sabrina Semprini,Louise Ashall,David G. Spiller,John J. Mullins,David A. Rand ,Julian R. E. Davis ,Michael R. H. White
PLOS Biology , 2011, DOI: 10.1371/journal.pbio.1000607
Abstract: In individual mammalian cells the expression of some genes such as prolactin is highly variable over time and has been suggested to occur in stochastic pulses. To investigate the origins of this behavior and to understand its functional relevance, we quantitatively analyzed this variability using new mathematical tools that allowed us to reconstruct dynamic transcription rates of different reporter genes controlled by identical promoters in the same living cell. Quantitative microscopic analysis of two reporter genes, firefly luciferase and destabilized EGFP, was used to analyze the dynamics of prolactin promoter-directed gene expression in living individual clonal and primary pituitary cells over periods of up to 25 h. We quantified the time-dependence and cyclicity of the transcription pulses and estimated the length and variation of active and inactive transcription phases. We showed an average cycle period of approximately 11 h and demonstrated that while the measured time distribution of active phases agreed with commonly accepted models of transcription, the inactive phases were differently distributed and showed strong memory, with a refractory period of transcriptional inactivation close to 3 h. Cycles in transcription occurred at two distinct prolactin-promoter controlled reporter genes in the same individual clonal or primary cells. However, the timing of the cycles was independent and out-of-phase. For the first time, we have analyzed transcription dynamics from two equivalent loci in real-time in single cells. In unstimulated conditions, cells showed independent transcription dynamics at each locus. A key result from these analyses was the evidence for a minimum refractory period in the inactive-phase of transcription. The response to acute signals and the result of manipulation of histone acetylation was consistent with the hypothesis that this refractory period corresponded to a phase of chromatin remodeling which significantly increased the cyclicity. Stochastically timed bursts of transcription in an apparently random subset of cells in a tissue may thus produce an overall coordinated but heterogeneous phenotype capable of acute responses to stimuli.
Gene expression profiling of liver from dairy cows treated intra-mammary with lipopolysaccharide
Li Jiang, Peter S?rensen, Christine R?ntved, Lotte Vels, Klaus L Ingvartsen
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-443
Abstract: Approximately 20% target transcripts were differentially expressed and eight co-expression clusters were identified. Each cluster had a unique time-dependent expression profile and consisted of genes involved in different biological processes. Our findings suggest that APR in the liver is triggered by the activation of signaling pathways that are involved with common and hepatic-specific transcription factors and pro-inflammatory cytokines. These mediators in turn stimulated or repressed the expression of genes encoding acute phase proteins (APP), collectins, complement components, chemokines, cell adhesion molecules and key metabolic enzymes during the APR. Hormones, anti-inflammatory and other hypothalamus-pituitary-adrenal axis (HPAA) linked mediators also seemed to participate in APR.Performing global gene expression analysis on liver tissue from IM LPS treated cows verified that the liver plays a major role in the APR of E. coli mastitis, and that the bovine hepatic APR follows the same pattern as other mammals when they are challenged with LPS. Our work presents the first insight into the dynamic changes in gene expression in the liver that influences the induction, kinetics and clinical outcome of the APR in dairy cows.Mastitis caused by Escherichia coli (E. coli) is a common disease in lactating dairy cows. During infection, lipopolysaccharide (LPS) released from the cell wall of E. coli rapidly induces a sophisticated inflammatory response. Locally it is characterized by recruiting leukocytes especially neutrophils to the injured mammary tissue, as well as activation of macrophages in the mammary gland to produce pro-inflammatory cytokines [1]. These pro-inflammatory cytokines include tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6), which have profound roles in the inflammatory response. Systemic consequences are observed as the acute phase response (APR) phenomena such as fever, leukocytosis and altered plasma concentrati
The Transcription Factor C/EBP-β Mediates Constitutive and LPS-Inducible Transcription of Murine SerpinB2  [PDF]
Ekemini A. Udofa, Brett W. Stringer, Padmaja Gade, Donna Mahony, Marguerite S. Buzza, Dhananjaya V. Kalvakolanu, Toni M. Antalis
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057855
Abstract: SerpinB2 or plasminogen activator inhibitor type 2 (PAI-2) is highly induced in macrophages in response to inflammatory stimuli and is linked to the modulation of innate immunity, macrophage survival, and inhibition of plasminogen activators. Lipopolysaccharide (LPS), a potent bacterial endotoxin, can induce SerpinB2 expression via the toll-like receptor 4 (TLR4) by ~1000-fold over a period of 24 hrs in murine macrophages. To map the LPS-regulated SerpinB2 promoter regions, we transfected reporter constructs driven by the ~5 kb 5'-flanking region of the murine SerpinB2 gene and several deletion mutants into murine macrophages. In addition, we compared the DNA sequence of the murine 5′ flanking sequence with the sequence of the human gene for homologous functional regulatory elements and identified several regulatory cis-acting elements in the human SERPINB2 promoter conserved in the mouse. Mutation analyses revealed that a CCAAT enhancer binding (C/EBP) element, a cyclic AMP response element (CRE) and two activator protein 1 (AP-1) response elements in the murine SerpinB2 proximal promoter are essential for optimal LPS-inducibility. Electrophoretic mobility shift (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated that LPS induces the formation of C/EBP-β containing complexes with the SerpinB2 promoter. Importantly, both constitutive and LPS-induced SerpinB2 expression was severely abrogated in C/EBP-β-null mouse embryonic fibroblasts (MEFs) and primary C/EBP-β-deficient peritoneal macrophages. Together, these data provide new insight into C/EBP-β-dependent regulation of inflammation-associated SerpinB2 expression.
LPS Regulates SOCS2 Transcription in a Type I Interferon Dependent Autocrine-Paracrine Loop  [PDF]
Jin Hu, DaoHua Lou, Berit Carow, Malin E. Winerdal, Martin Rottenberg, Ann-Charlotte Wikstr?m, Gunnar Norstedt, Ola Winqvist
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030166
Abstract: Recent studies suggest that SOCS2 is involved in the regulation of TLR signaling. In this study, we found that the expression of SOCS2 is regulated in human monocyte-derived DC by ligands stimulating TLR2, 3, 4, 5, 8 and 9 signaling. SOCS2 induction by LPS was dependent on the type I IFN regulated transcription factors IRF1 and IRF3 as shown by using silencing RNAs for IRFs. Blocking endogenous type I IFN signaling, by neutralizing antibodies to the receptor IFNAR2, abolished SOCS2 mRNA expression after TLR4 stimulation. Transcription factors STAT3, 5 and 6 displayed putative binding sites in the promoter regions of the human SOCS2 gene. Subsequent silencing experiments further supported that STAT3 and STAT5 are involved in LPS induced SOCS2 regulation. In mice we show that SOCS2 mRNA induction is 45% lower in bone marrow derived macrophages derived from MyD88?/? mice, and do not increase in BMMs from IRF3?/? mice after BCG infection. In conclusion, our results suggest that TLR4 signaling indirectly increases SOCS2 in late phase mainly via the production of endogenous type I IFN, and that subsequent IFN receptor signaling activates SOCS2 via STAT3 and STAT5.
Cardiac force-frequency relationship and frequency-dependent acceleration of relaxation are impaired in LPS-treated rats
Olivier Joulin, Sylvestre Marechaux, Sidi Hassoun, David Montaigne, Steve Lancel, Remi Neviere
Critical Care , 2009, DOI: 10.1186/cc7712
Abstract: Following LPS injection, changes in force-frequency relationship and FDAR were studied in cardiomyocytes, isolated hearts and in vivo by echocardiography. Calcium uptake and phosphatase activities were studied in sarcoplasmic reticulum (SR) vesicle preparations. Western blots of phospholamban and calcium/calmodulin-dependent protein kinase II, and serine/threonine phosphatase activity were studied in heart preparations.In cardiomyocytes and isolated heart preparations, reductions in time constant of relaxation (τ) and time to 50% relaxation at increasing rate of pacing were blunted in LPS-treated rats compared with controls. Early diastolic velocity of the mitral annulus (Ea), a relaxation parameter which correlates in vivo with τ, was reduced in LPS rats compared with control rats. LPS impaired SR calcium uptake, reduced phospholamban phosphorylation and increased serine/threonine protein phosphatase activity. In vivo inhibition of phosphatase activity partially restored FDAR, reduced phosphatase activity and prevented phospholamban dephosphorylation in LPS rat hearts.LPS impaired phospholamban phosphorylation, cardiac force-frequency relationship and FDAR. Disruption of frequency-dependent acceleration of LV relaxation, which normally participates in optimal heart cavity filling, may be detrimental in sepsis, which is typically associated with elevated heart rates and preload dependency.Apart from the Frank-Starling mechanism, force-frequency relationship represents a major intrinsic regulatory factor that is essential for the immediate adjustment of cardiac contractile function to rapid changing requirements of blood supply. The frequency-dependent gain in contractility is an intrinsic property of cardiac muscle present in all mammals and allows for greater contractile force [1]. Not only does the heart generally beat stronger when it is stimulated to contract faster, the kinetic of contraction is also accelerated, that is, the frequency-dependent acceleration of
Differentiation Driven Changes in the Dynamic Organization of Basal Transcription Initiation  [PDF]
Giuseppina Giglia-Mari,Arjan F. Theil,Pierre-Olivier Mari,Sophie Mourgues,Julie Nonnekens,Lise O. Andrieux,Jan de Wit,Catherine Miquel,Nils Wijgers,Alex Maas,Maria Fousteri,Jan H. J. Hoeijmakers,Wim Vermeulen
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000220
Abstract: Studies based on cell-free systems and on in vitro–cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion. This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent. Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs. This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies.
Differentiation Driven Changes in the Dynamic Organization of Basal Transcription Initiation  [PDF]
Giuseppina Giglia-Mari ,Arjan F. Theil equal contributor,Pierre-Olivier Mari equal contributor,Sophie Mourgues,Julie Nonnekens,Lise O. Andrieux,Jan de Wit,Catherine Miquel,Nils Wijgers,Alex Maas,Maria Fousteri,Jan H. J. Hoeijmakers,Wim Vermeulen
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000220
Abstract: Studies based on cell-free systems and on in vitro–cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion. This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent. Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs. This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.