Sample records for box-1 protein lipopolysaccharide-binding

  1. Significance of lipopolysaccharide-binding protein (an acute phase protein) in monitoring critically ill patients

    Prucha, Miroslav; Herold, Ivan; Zazula, Roman; Dubska, Ladislava; Dostal, Miroslav; Hildebrand, Thomas; Hyanek, Josef


    Introduction The present study was conducted to assess the value of serum concentration of lipopolysaccharide-binding protein (LBP) in patients with systemic inflammatory response syndrome (SIRS), sepsis and septic shock with respect to its ability to differentiate between infectious and noninfectious etiologies in SIRS and to predict prognosis. Methods This prospective cohort study was conducted in a multidisciplinary intensive care unit. Sixty-eight patients, admitted consecutively to the i...

  2. Diagnostic value of lipopolysaccharide-binding protein and procalcitonin for sepsis diagnosis in forensic pathology

    Augsburger, Marc; Iglesias, Katia; Bardy, Daniel; Mangin, Patrice; Palmiere, Cristian


    The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans,...

  3. Interleukin 6 and lipopolysaccharide binding protein - markers of inflammation in acute appendicitis.

    Brănescu, C; Serban, D; Dascălu, A M; Oprescu, S M; Savlovschi, C


    The rate of incidence of acute appendicitis is 12% in the case of male patients and 25% in case of women, which represents about 7% of the world population. The appendectomy rate has remained constant (i.e. 10 out of 10,000 patients per year). Appendicitis most often occurs in patients aged between 11-40 years, on the threshold between the third and fourth decades, the average age being 31.3 years. Since the first appendectomy performed by Claudius Amyand (1681/6 -1740), on December, 6th, 1735 to our days, i.e., 270 years later, time has confirmed the efficiency of both the therapy method and the surgical solution. The surgical cure in case of acute appendicitis has proved to be acceptable within the most widely practised techniques in general surgery. The variety of clinical forms has reached all age ranges, which in its turn has resulted in a large number of semiotic signs. In the case of acute appendicitis, interdisciplinarity has allowed the transfer of concept and methodology transfer among many areas of expertise, aimed at a better, minute understanding of the inflammatory event itself. Acute appendicitis illustrates inflammation development at digestive level and provides for a diagnostic and paraclinical exploration which continually upgrades. The recent inclusion in the studies of the Lipopolysaccharide binding protein (LBP)- type inflammation markers has laid the foundation of the latter's documented presence in the case of acute appendicitis-related inflammation. Proof of the correlation between the histopathological, clinical and evolutive forms can be found by identifying and quantifying these inflammation markers. The importance of studying inflammation markers allows us to conduct studies going beyond the prognosis of the various stages in which these markers were identified. The present article shows the results of a 1-year monitoring of the inflammation markers' values for Interleukin-6 and Lipopolysaccharide binding protein (LBP)-types, both pre

  4. The level of lipopolysaccharide-binding protein is significantly increased in plasma in patients with the systemic inflammatory response syndrome.

    Myc, A; Buck, J.; Gonin, J.; Reynolds, B.; Hammerling, U; Emanuel, D


    Currently, there is no way to predict with a high degree of sensitivity and specificity which patients are likely to develop systemic inflammatory response syndrome (SIRS) following systemic infection, trauma, organ rejection, or blood loss. The level of human lipopolysaccharide-binding protein (LBP) was determined in the plasma of 22 patients with a clinical diagnosis of early SIRS. Twenty-nine plasma samples from healthy volunteers were used as controls. The mean level of LBP in the plasma ...

  5. Lipopolysaccharide-binding protein for monitoring of postoperative sepsis: complemental to C-reactive protein or redundant?

    Klaus Tschaikowsky

    Full Text Available INTRODUCTION: To prospectively evaluate the performance of Lipopolysaccharide-Binding Protein (LBP in prediction of hospital mortality and its correlation to C-reactive Protein (CRP, we studied sixty consecutive, postoperative patients with sepsis admitted to the university hospital intensive care unit. MEASUREMENTS AND METHODS: Plasma LBP and CRP were serially measured from day(d1 (onset of sepsis to d14 in parallel with clinical data until d28. Predictive value and correlation of LBP and CRP were analyzed by Receiver Operating Characteristic (ROC curve analysis and Pearson's test, respectively. MAIN RESULTS: LBP and CRP showed the highest levels on d2 or d3 after the onset of sepsis with no significant difference between survivors and nonsurvivors. Only at d7, nonsurvivors had significantly (p = .03 higher levels of CRP than survivors. Accordingly, in ROC analysis, concentration of CRP and LBP on d7 poorly discriminated survivors from nonsurvivors (area under curve = .62 and .55, respectively without significant difference between LBP- and CRP-ROC curves for paired comparison. LBP and CRP plasma levels allocated to quartiles correlated well with each other (r(2 = .95; p = .02. Likewise, changes in plasma concentrations of LBP and CRP from one observation to the next showed a marked concordance as both parameters concomitantly increased or decreased in 76% of all cases. CONCLUSIONS: During the first 14 days of postoperative sepsis, LBP plasma concentrations showed a time course that was very similar to CRP with a high concordance in the pattern of day-to-day changes. Furthermore, like CRP, LBP does not provide a reliable clue for outcome in this setting.

  6. High mobility group box-1 protein in patients with suspected community-acquired infections and sepsis: a prospective study

    Gaïni, Shahin; Pedersen, Svend Stenvang; Koldkjaer, Ole Graesbøll;


    INTRODUCTION: Sepsis is a serious condition with a significant morbidity and mortality. New insight into the immunopathogenesis of sepsis could promote the development of new strategies for diagnosis and therapy. High mobility group box-1 protein (HMGB1) has been known for many years as a nuclear...... a department of internal medicine were included in the study in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score, and mortality on day 28 were recorded. Plasma and serum were sampled at the time of admission. HMGB1...... non-infected patients and all infected patients, the area under the curve for HMGB1 was 0.59 (P < 0.0001). HMGB1 correlated only weakly to levels of white blood cell count, neutrophils, C-reactive protein, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein (P < 0.001). HMGB1 did not...

  7. Lipopolysaccharide-binding protein of Bombyx mori participates in a hemocyte-mediated defense reaction against gram-negative bacteria.

    Koizumi, N; Imai, Y; Morozumi, A; Imamura, M; Kadotani, T; Yaoi, K; Iwahana, H; Sato, R


    BmLBP is a lipopolysaccharide-binding protein in B. mori and participates in bacterial clearance in vivo. Here, we investigated the function of BmLBP more specifically. More than 90% of injected gram-negative rough strains to which BmLBP binds were removed from the plasma within 30 min post-injection, whereas it required 8h for the clearance of smooth strains to which BmLBP does not bind. Observation of the hemocoel after the injection of Escherichia coli rough strain showed that melanized nodules were formed at 30 min post-injection when the clearance of injected E. coli cells had occurred. Fluorescence microscope observation revealed that E. coli cells were actually trapped in the nodules formed in vivo. Furthermore, plasma pre-treated E. coli rough cells (BmLBP bound) added to hemocytes isolated in vitro caused vigorous hemocyte aggregations with the bacteria, while plasma pre-treated smooth cells did not. The formation of aggregates was inhibited by anti-BmLBP serum pre-treatment, suggesting that BmLBP causes the clearance of bacteria by promoting hemocyte nodule formation. PMID:12770298

  8. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte;


    Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study in...... closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep into...... LBP together with other proteins acting in the innate immune response of the gut, such as lysozyme, defensins and intelectin....

  9. Structural and Functional Features of a Developmentally Regulated Lipopolysaccharide-Binding Protein

    Krasity, Benjamin C.; Troll, Joshua V.; Lehnert, Erik M.; Hackett, Kathleen T.; Dillard, Joseph P.; Apicella, Michael A.; Goldman, William E.


    ABSTRACT Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has not been well characterized. Using the Euprymna scolopes-Vibrio fischeri model, we analyzed the structure and function of an LBP family protein, E. scolopes LBP1 (EsLBP1), and provide evidence for its role in triggering a symbiont-induced host developmental program. Previous studies showed that, during initial host colonization, the LPS of V. fischeri synergizes with peptidoglycan (PGN) monomer to induce morphogenesis of epithelial tissues of the host animal. Computationally modeled EsLBP1 shares some but not all structural features of mammalian LBPs that are thought important for LPS binding. Similar to human LBP, recombinant EsLBP1 expressed in insect cells bound V. fischeri LPS and Neisseria meningitidis lipooligosaccharide (LOS) with nanomolar or greater affinity but bound Francisella tularensis LPS only weakly and did not bind PGN monomer. Unlike human LBP, EsLBP1 did not bind N. meningitidis LOS:CD14 complexes. The eslbp1 transcript was upregulated ~22-fold by V. fischeri at 24 h postinoculation. Surprisingly, this upregulation was not induced by exposure to LPS but, rather, to the PGN monomer alone. Hybridization chain reaction-fluorescent in situ hybridization (HCR-FISH) and immunocytochemistry (ICC) localized eslbp1 transcript and protein in crypt epithelia, where V. fischeri induces morphogenesis. The data presented here provide a window into the evolution of LBPs and the scope of their roles in animal symbioses. PMID:26463160

  10. Molecular Properties of Guar Gum and Pectin Modify Cecal Bile Acids, Microbiota, and Plasma Lipopolysaccharide-Binding Protein in Rats.

    Ghaffarzadegan, Tannaz; Marungruang, Nittaya; Fåk, Frida; Nyman, Margareta


    Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin-two fibers with distinct functional characteristics-affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ω-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ω-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced

  11. Molecular Properties of Guar Gum and Pectin Modify Cecal Bile Acids, Microbiota, and Plasma Lipopolysaccharide-Binding Protein in Rats.

    Tannaz Ghaffarzadegan

    Full Text Available Bile acids (BAs act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin-two fibers with distinct functional characteristics-affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM or high-methoxylated (HM pectin, and low-, medium-, or high-molecular-weight (MW guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ω-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ω-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high

  12. The lipopolysaccharide-binding protein is a secretory class 1 acute-phase protein whose gene is transcriptionally activated by APRF/STAT/3 and other cytokine-inducible nuclear proteins.

    Schumann, R.R.; Kirschning, C.J.; Unbehaun, A; Aberle, H P; Knope, H P; Lamping, N; Ulevitch, R J; Herrmann, F.


    Acute-phase reactants (APRs) are proteins synthesized in the liver following induction by interleukin-1 (IL-1), IL-6, and glucocorticoids, involving transcriptional gene activation. Lipopolysaccharide-binding protein (LBP) is a recently identified hepatic secretory protein potentially involved in the pathogenesis of sepsis, capable of binding the bacterial cell wall product endotoxin and directing it to its cellular receptor, CD14. In order to examine the transcriptional induction mechanisms ...

  13. Prognostic Value And Daily Trend Of Interleukin-6, Neutrophil CD64 Expression, C-Reactive Protein And Lipopolysaccharide-Binding Protein In Critically Ill Patients: Reliable Predictors Of Outcome Or Not?

    Djordjevic Dragan


    Full Text Available Background: Severe sepsis and/or trauma complicated by multiple organ dysfunction syndrome are the leading causes of death in critically ill patients. The aim of this prospective single-centre study was to assess the prognostic value and daily trend of interleukin-6 (IL-6, neutrophil CD64 expression, C-reactive protein (CRP and lipopolysaccharide-binding protein (LBP regarding outcome in critically ill patients with severe trauma and/or severe sepsis. Outcome measure was hospital mortality.

  14. A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study

    Gaïni, Shahin; Koldkjaer, Ole G; Møller, Holger J;


    immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included...

  15. Comparison of the effect of recombinant bovine wild and mutant lipopolysaccharide-binding protein in lipopolysaccharide-challenged bovine mammary epithelial cells.

    Li, Xiaojuan; Li, Lian; Sun, Yu; Wu, Jie; Wang, Genlin


    Lipopolysaccharide (LPS)-binding protein (LBP) plays a crucial role in the recognition of bacterial components, such as LPS that causes an immune response. The aim of this study was to compare the different effects of recombinant bovine wild LBP and mutant LBP (67 Ala → Thr) on the LPS-induced inflammatory response of bovine mammary epithelial cells (BMECs). When BMECs were treated with various concentrations of recombinant bovine lipopolysaccharide-binding protein (RBLBP) (1, 5, 10, and 15 μg/mL) for 12 h, RBLBP of 5 μg/mL increased the apoptosis of BMECs induced by LPS without cytotoxicity, and mutant LBP resulted in a higher cell apoptosis than wild LBP did. By gene-chip microarray and bioinformatics, the data identified 2306 differentially expressed genes that were changed significantly between the LPS-induced inflamed BMECs treated with 5 μg/mL of mutant LBP and the BMECs only treated with 10 μg/mL of LPS (fold change ≥2). Meanwhile, 1585 genes were differently expressed between the inflamed BMECs treated with 5 μg/mL of wild LBP and 10 μg/mL of LPS-treated BMECs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these differentially expressed genes were involved in different pathways that regulate the inflammation response. It predicted that carriers of this mutation increase the risk for a more severe inflammatory response. Our study provides an overview of the gene expression profile between wild LBP and mutant LBP on the LPS-induced inflammatory response of BMECs, which will lead to further understanding of the potential effects of LBP mutations on bovine mammary glands. PMID:26813383

  16. High-mobility group box 1 protein and its role in severe acute pancreatitis

    Shen, Xiao; Li, Wei-Qin


    The high mobility group box 1 (HMGB1), which belongs to the subfamily of HMG-1/-2, is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da. HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases. Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis. Acute pancreatitis is an acute inflammatory process of the pancreas (duration of less...

  17. Identification of the Zinc Finger Protein ZRANB2 as a Novel Maternal Lipopolysaccharide-binding Protein That Protects Embryos of Zebrafish against Gram-negative Bacterial Infections.

    Wang, Xia; Du, Xiaoyuan; Li, Hongyan; Zhang, Shicui


    Zinc finger ZRANB2 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that ZRANB2 is a newly identified LPS-binding protein present abundantly in the eggs/embryos of zebrafish. We also show that recombinant ZRANB2 (rZRANB2) acts as a pattern recognition receptor capable of identifying the bacterial signature molecule LPS as well as binding the Gram-negative bacteria Escherichia coli, Vibrio anguilarum, and Aeromonas hydrophila and functions as an antibacterial effector molecule capable of directly killing the bacteria. Furthermore, we reveal that N-terminal residues 11-37 consisting of the first ZnF_RBZ domain are indispensable for ZRANB2 antimicrobial activity. Importantly, microinjection of rZRANB2 into early embryos significantly enhanced the resistance of the embryos against pathogenic A. hydrophila challenge, and this enhanced bacterial resistance was markedly reduced by co-injection of anti-ZRANB2 antibody. Moreover, precipitation of ZRANB2 in the embryo extracts by preincubation with anti-ZRANB2 antibody caused a marked decrease in the antibacterial activity of the extracts against the bacteria tested. In addition, the N-terminal peptide Z1/37 or Z11/37 with in vitro antibacterial activity also promoted the resistance of embryos against A. hydrophila, but the peptide Z38/198 without in vitro antibacterial activity did not. Collectively, these results indicate that ZRANB2 is a maternal LPS-binding protein that can protect the early embryos of zebrafish against pathogenic attacks, a novel role ever assigned to ZRANB2 proteins. This work also provides new insights into the immunological function of the zinc finger proteins that are widely distributed in various animals. PMID:26740623


    The high mobility group box-1 protein (HMGB-1) is a well-characterized nuclear protein recently shown to be involved in endotoxin-induced inflammation and injury. Studies have linked HMGB-1 release to the production of pro-inflammatory cytokines; however, a role for HMGB-1 in other disorders involvi...

  19. Cloning and characterization of two lipopolysaccharide-binding protein/bactericidal permeability-increasing protein (LBP/BPI) genes from the sea cucumber Apostichopus japonicus with diversified function in modulating ROS production.

    Shao, Yina; Li, Chenghua; Che, Zhongjie; Zhang, Pengjuan; Zhang, Weiwei; Duan, Xuemei; Li, Ye


    Lipopolysaccharide-binding protein and bactericidal permeability-increasing protein (LBP/BPI) play crucial role in modulating cellular signals in response to Gram-negative bacteria infection. In the present study, two isoforms of LBP/BPI genes (designated as AjLBP/BPI1 and AjLBP/BPI2, respectively) were cloned from the sea cucumber Apostichopus japonicus by RACE approach. The full-length cDNAs of AjLBP/BPI1 and AjLBP/BPI2 were of 1479 and 1455 bp and encoded two secreted proteins of 492 and 484 amino acid residues, respectively. Signal peptide, two BPI/LBP/CETP and one central domain were totally conserved in the deduced amino acid of AjLBP/BPI1 and AjLBP/BPI2. Phylogentic analysis further supported that AjLBP/BPI1 and AjLBP/BPI2 belonged to new members of invertebrates LBP/BPI family. Spatial expression analysis revealed that both AjLBP/BPI1 and AjLBP/BPI2 were ubiquitously expressed in all examined tissues with the larger magnitude in AjLBP/BPI1. The Vibrio splenfidus challenge and LPS stimulation could significantly up-regulate the mRNA expression of both AjLBP/BPI1 and AjLBP/BPI2, with the increase of AjLBP/BPI2 expression occurred earlier than that of AjLBP/BPI1. More importantly, we found that LPS induced ROS production was markedly depressed after AjLBP/BPI1 knock-down, but there was no significant change by AjLBP/BPI2 silencing. Consistently, the expression level of unclassified AjToll, not AjTLR3, was tightly correlated with that of AjLBP/BPI1. Silencing the AjToll also depressed the ROS production in the cultured coelomocytes. All these results indicated that AjLBP/BPI1 and AjLBP/BPI2 probably played distinct roles in bacterial mediating immune response in sea cucumber, and AjLBP/BPI1 depressed coelomocytes ROS production via modulating AjToll cascade. PMID:25956196

  20. High Mobility Group Box1 Protein Is Involved in Endoplasmic Reticulum Stress Induced by Clostridium difficile Toxin A.

    Liu, Ji; Ma, Yi; Sun, Chun-Li; Li, Shan; Wang, Ju-Fang


    High Mobility Group Box1 (HMGB1), a damage-associated inflammatory factor, plays an important role in the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, the role of the HMGB1 in TcdA-induced ER stress was identified. Clostridium difficile toxin A is one of the major virulence factors of C. difficile infection (CDI) and has been proved to induce apoptotic cell death through ER stress. Our results showed that HMGB1 might play an important role in the TcdA-induced ER stress and unfolded protein response. HMGB1 activated molecular markers and induced the C/EBP homologous protein upregulation (CHOP). This study may provide the essential information for better understanding of the molecular mechanisms involved in CDI. PMID:27579314

  1. DMPD: Lipopolysaccharide-binding molecules: transporters, blockers and sensors. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 15241548 Lipopolysaccharide-binding molecules: transporters, blockers and sensors. ...binding molecules: transporters, blockers and sensors. PubmedID 15241548 Title Lipopolysaccharide-binding mo...lecules: transporters, blockers and sensors. Authors Chaby R. Publication Cell Mo

  2. High mobility group box-1 is phosphorylated by protein kinase C zeta and secreted in colon cancer cells

    Highlights: ► Specific enzyme for HMGB1 phosphorylation and its secretion is proposed. ► Inhibition of PKC-ζ leads to significant reduction of the secreted HMGB1. ► Phosphorylation of specific site of HMGB1 redirects its secretion in cancer cells. ► Activation of PKC-ζ in cancers explains the enhanced HMGB1 secretion. -- Abstract: High mobility group box-1 (HMGB1), a nuclear protein, is overexpressed and secreted in cancer cells. Phosphorylation on two different nuclear localization signal regions are known to be important for the nuclear-to-cytoplasmic transport and secretion of HMGB1. However, little is known about the biochemical mechanism of HMGB1 modifications and its subsequent secretion from cancer cells. To identify the specific enzyme and important sites for HMGB1 phosphorylation, we screened the protein kinase C (PKC) family in a colon cancer cell line (HCT116) for HMGB1 binding by pull-down experiments using a 3XFLAG-HMGB1 construct. Strong interactions between atypical PKCs (PKC-ζ, λ, and ι) and cytoplasmic HMGB1 were observed in HCT116 cells. We further identified the most critical PKC isotype that regulates HMGB1 secretion is PKC-ζ by using PKC inhibitors and siRNA experiments. The serine residues at S39, S53 and S181 of HMGB1 were related to enhancing HMGB1 secretion. We also demonstrated overexpression and activation of PKC-ζ in colon cancer tissues. Our findings suggest that PKC-ζ is involved in the phosphorylation of HMGB1, and the phosphorylation of specific serine residues in the nuclear localization signal regions is related to enhanced HMGB1 secretion in colon cancer cells.

  3. Effects of high-mobility group box 1 on the expression of Beclin-1 and LC3 proteins following hypoxia and reoxygenation injury in rat cardiomyocytes

    Xu, Weipan; Jiang, Hong; Hu, Xiaorong; Fu, Wenwen


    The mechanisms underlying autophagy during myocardial ischemia and reperfusion remain unclear. The present study investigated the relationship between high-mobility group box 1 protein (HMGB1) and autophagy in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. Neonatal rat cardiomyocytes were treated with recombinant HMGB1 (200 ng/L) or ammonium glycyrrhizinate (100 μM) at appropriate concentrations. Cell viabilities and lactate dehydrogenase (LDH) and creatine kinase (CK) activ...

  4. High mobility group box1 protein is involved in acute inflammation induced by Clostridium difficile toxin A.

    Liu, Ji; Zhang, Bei-Lei; Sun, Chun-Li; Wang, Jun; Li, Shan; Wang, Ju-Fang


    High mobility group box1 (HMGB1), as a damage-associated inflammatory factor, contributes to the pathogenesis of numerous chronic inflammatory and autoimmune diseases. In this study, we explored the role of HMGB1 in CDI (Clostridium difficile infection) by in vivo and in vitro experiments. Our results showed that HMGB1 might play an important role in the acute inflammatory responses to C. difficile toxin A (TcdA), affect early inflammatory factors, and induce inflammation via the HMGB1-TLR4 pathway. Our study provides the essential information for better understanding the molecular mechanisms of CDI and the potential new therapeutic strategies for the treatment of this infection. PMID:27151296

  5. Correlation between serum high-mobility group box-1 levels and high-sensitivity C-reactive protein and troponin I in patients with coronary artery disease



    The aim of this study was to evaluate the correlation between levels of serum high-mobility group box-1 (HMGB1) and high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin I in patients with coronary artery disease. The levels of serum HMGB1, hs-CRP and cardiac troponin I were measured in 98 patients with coronary artery disease and in 30 healthy subjects. The correlation between serum HMGB1 levels and hs-CRP and cardiac troponin I levels was analyzed. Serum HMGB1 levels in patients...

  6. The lipopolysaccharide-binding protein participating in hemocyte nodule formation in the silkworm Bombyx mori is a novel member of the C-type lectin superfamily with two different tandem carbohydrate-recognition domains.

    Koizumi, N; Imamura, M; Kadotani, T; Yaoi, K; Iwahana, H; Sato, R


    We recently isolated and characterized the lipopolysaccharide (LPS)-binding protein, BmLBP, from the larval hemolymph of the silkworm Bombyx mori. BmLBP is a pattern recognition molecule that recognizes the lipid A portion of LPS and participates in a cellular defense reaction. This paper describes the cDNA cloning of BmLBP. The deduced amino acid sequence of BmLBP revealed that BmLBP is a novel member of the C-type lectin superfamily with a unique structural feature that consists of two different carbohydrate-recognition domains in tandem, a short and a long form. PMID:9989592

  7. High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo.

    Antoine, Daniel J; Williams, Dominic P; Kipar, Anja; Jenkins, Rosalind E; Regan, Sophie L; Sathish, Jean G; Kitteringham, Neil R; Park, B Kevin


    Drug-induced hepatotoxicity represents a major clinical problem and an impediment to new medicine development. Serum biomarkers hold the potential to provide information about pathways leading to cellular responses within inaccessible tissues, which can inform the medicinal chemist and the clinician with respect to safe drug design and use. Hepatocyte apoptosis, necrosis, and innate immune activation have been defined as features of the toxicological response associated with the hepatotoxin acetaminophen (APAP). Within this investigation, we have unambiguously identified and characterized by liquid chromatography-tandem mass spectrometry differing circulating molecular forms of high-mobility group box-1 protein (HMGB1) and keratin-18 (K18), which are linked to the mechanisms and pathological changes induced by APAP in the mouse. Hypoacetylated HMGB1 (necrosis indicator), caspase-cleaved K18 (apoptosis indicator), and full-length K18 (necrosis indicator) present in serum showed strong correlations with the histological time course of cell death and was more sensitive than alanine aminotransferase activity. We have further identified a hyperacetylated form of HMGB1 (inflammatory indicator) in serum, which indicated that hepatotoxicity was associated with an inflammatory response. The inhibition of APAP-induced apoptosis and K18 cleavage by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethyl ketone are associated with increased hepatic damage, by a shift to necrotic cell death only. These findings illustrate the initial verification of K18 and HMGB1 molecular forms as serum-based sensitive tools that provide insights into the cellular dynamics involved in APAP hepatotoxicity within an inaccessible tissue. Based on these findings, potential exists for the qualification and measurement of these proteins to further assist in vitro, in vivo, and clinical bridging in toxicological research. PMID:19783637

  8. Effects of high-mobility group box 1 on the expression of Beclin-1 and LC3 proteins following hypoxia and reoxygenation injury in rat cardiomyocytes.

    Xu, Weipan; Jiang, Hong; Hu, Xiaorong; Fu, Wenwen


    The mechanisms underlying autophagy during myocardial ischemia and reperfusion remain unclear. The present study investigated the relationship between high-mobility group box 1 protein (HMGB1) and autophagy in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. Neonatal rat cardiomyocytes were treated with recombinant HMGB1 (200 ng/L) or ammonium glycyrrhizinate (100 μM) at appropriate concentrations. Cell viabilities and lactate dehydrogenase (LDH) and creatine kinase (CK) activity levels were measured. HMGB1, LC3 and Beclin-1 expression were assessed by Western blot. The results demonstrated that HMGB1-induced myocardial cells have increased levels of Beclin-1 protein and even higher levels of LC3 protein, while HMGB1-inhibited myocardial cells have decreased levels of Beclin-1 and LC3 proteins. In addition, HMGB1 induction significantly increased LDH and CK levels in the cell culture medium; the inhibition of HMGB1 significantly reduced LDH and CK expression in cardiomyocyte culture medium. In conclusion, the results of the present study suggest that HMGB1 is able to regulate Beclin-1 and LC3 levels following hypoxia and reoxygenation injury in rat cardiomyocytes. PMID:25664043

  9. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.

    Zhang, Ting; Hu, Xiaorong; Cai, Yuli; Yi, Bo; Wen, Zhongyuan


    Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1. PMID:24420848

  10. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong


    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  11. Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation

    X-ray radiotherapy activates tumor antigen-specific T-cell responses, and increases in the serum levels of high mobility group box 1 (HMGB1) induced by X-ray irradiation play a pivotal role in activating anti-tumor immunity. Here, we examined whether carbon-ion beams, as well as X-rays, can induce HMGB1 release from human cancer cell lines. The study examined five human cancer cell lines: TE2, KYSE70, A549, NCI-H460 and WiDr. The proportion of cells surviving X- or carbon-ion beam irradiation was assessed in a clonogenic assay. The D10, the dose at which 10% of cells survive, was calculated using a linear–quadratic model. HMGB1 levels in the culture supernatants were assessed by an ELISA. The D10 dose for X-rays in TE2, KYSE70, A549, NCI-H460 and WiDr cells was 2.1, 6.7, 8.0, 4.8 and 7.1 Gy, respectively, whereas that for carbon-ion beams was 0.9, 2.5, 2.7, 1.8 and 3.5 Gy, respectively. X-rays and carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of A549, NCI-H460 and WiDr cells at 72 h post-irradiation with a D10 dose. Furthermore, irradiation with X-rays or carbon-ion beams significantly increased HMGB1 levels in the culture supernatants of all five cell lines at 96 h post-irradiation. There was no significant difference in the amount of HMGB1 induced by X-rays and carbon-ion beams at any time-point (except at 96 h for NCI-H460 cells); thus we conclude that comparable levels of HMGB1 were detected after irradiation with iso-survival doses of X-rays and carbon-ion beams. (author)

  12. Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

    Koide Michio


    Full Text Available Abstract Background Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods Nuclear deoxyribonucleic acid (DNA fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP-biotin nick end labeling method (TUNEL method and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1 protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a

  13. Comparison of Lipopolysaccharide binding protein and C-reactive protein gene expression levels in a Rat model of induced Atherosclerosis

    Kholoud S. Ramadan*1; Rasha E. Hassan1: Abd El Rahman B. Abd El Ghaffar1 and Asmaa A. Deghedy1


    Full Text Available Atherosclerosis is an inflammatory disease characterized by the accumulation of lipids within arterial walls that eventually go on to form plaques, which can cause narrowing, hardening, and/or complete blockage of arteries. This study was designed to examine the cholesterol feeding induction of cardiovascular diseases exemplified by atherosclerosis in rat and induction of CRP, LBP, SAP and P4H on the transcriptional activity of the inflammation / related gene expression by a semi-quantitative RT-PCR in liver and heart tissues, and make comparison between CRP and LBP as biomarker for atherosclerosis. Material & Methods: Experimental Rats were fed with cholesterol diet (2.5% pure (wt/wt cholesterol, 1% cholic acid and 5% oil and sacrificed after 18 weeks of feeding. Results: Histopathological examination for heart showed fatty cells deposition in atherogenic rats. Expression pattern of CRP, LBP, SAP & P4H genes were investigated, in liver and heart, these genes were highly expressed while some of them showed no expression pattern in heart tissues.

  14. High-mobility group box-1 in sterile inflammation.

    Tsung, A; Tohme, S; Billiar, T R


    High-mobility group box 1 (HMGB1) was originally defined as a ubiquitous nuclear protein, but it was later determined that the protein has different roles both inside and outside of cells. Nuclear HMGB1 regulates chromatin structure and gene transcription, whereas cytosolic HMGB1 is involved in inflammasome activation and autophagy. Extracellular HMGB1 has drawn attention because it can bind to related cell signalling transduction receptors, such as the receptor for advanced glycation end products, Toll-like receptor (TLR)2, TLR4 and TLR9. It also participates in the development and progression of a variety of diseases. HMGB1 is actively secreted by stimulation of the innate immune system, and it is passively released by ischaemia or cell injury. This review focuses on the important role of HMGB1 in the pathogenesis of acute and chronic sterile inflammatory conditions. Strategies that target HMGB1 have been shown to significantly decrease inflammation in several disease models of sterile inflammation, and this may represent a promising clinical approach for treatment of certain conditions associated with sterile inflammation. PMID:24935761

  15. [Analysis of the impact of heparin on the affinity of high mobility group box-1 protein and the receptor of advanced glycation end products by surface plasmon resonance technology].

    Ling, Yan; Wang, Chun-You; Yang, Zhi-Yong


    To investigate the affinity constants of heparin with high mobility group protein 1(HMGB1) and HMGB1 with the receptor of advanced glycation end products (RAGE) and to analyze the impact of heparin on the affinity of HMGB1 and RAGE, the standard BIAcore amine coupling chemistry protocol using EDC and NHS was employed for immobilizing. Surface plasmon resonance biosensor technology was used to detect the affinity constants of heparin/HMGB1, HMGB1/RAGE and heparin/ RAGE. Binding analysis was used to investigate the impact of heparin on the affinity of HMGB1 and RAGE. After the immobilization, 9 000 and 5 000 RU rise of HMGB1 and RAGE respectively were obtained. These meant that the immobilized values of HMGB1 and RAGE were about 9 and 5 ng x mm(-2) respectively. The kinetic constants were k(a) = 1.78 x 10(5) L x mol(-1) x s(-1), kd = 8.02 x 10(-4) s(-1), and the affinity constants were KA = 2.22 x 10(8) L x mol(-1), the equilibrium dissociation constant K(D) = 4.5 x 10(-9) mol x L(-1) for heparin and HMGB1; while the kinetic constants were k(a) = 1.85 x 10(3) L x mol(-1) x s(-1), k(d) = 1.81 x 10(-4) s(-1), K(A) = 1.02 x 10(7) L x mol(-1), K(D) = 9.77 x 10(-8) mol x L(-1) for HMGB1 and RAGE; there was very low affinity of heparin with RAGE. The highest concentration of 10 000 u x L(-1) of heparin in this experiment did not reach the saturation with HMGB1. After 50 mg x L(-1) of HMGB1 was mixed with heparin of 50, 100, 1 000, 10 000 u x L(-1), the combining amount of HMGB1 and RAGE declined from 100 to 50 RU. But there were no significant differences between different concentrations of heparin. It was concluded that heparin can combine with HMGB1 and affect the affinity of HMGB1/RAGE. In addition, this impact was not in a dose-dependent manner. PMID:20101991

  16. 高迁移率族蛋白B1在创伤免疫功能紊乱中的作用及其调节机制%The potential role of high mobility group box 1 protein in immune dysfunction and its regulatory mechanism after major trauma

    姚咏明; 林洪远


    Objective To investigate the potential effect of high mobility group box 1 protein (HMGB1) on host immune response and its molecular regulation mechanism as well as its interventional pathway following major burns/trauma. Methods With both animal experiments and clinical investigation, serial studies were conducted to observe the effects of HMGB1 on changes in immune function of T lymphoeytes, dendritic cells, and macrophages both in vivo and in vitro. Results It was found that thermal injury or trauma induced a delayed and persistent increase in HMGB1 expression as well as its release in various tissues.HMGB1 formation could markedly influence the cell-mediated immunity, including the changes in T lymphocytes, dendritic cells, and macrophages following major trauma or burns. These effects were closely related with dysfunction of various organs in the course of sepsis. Conclusion These data proved that HMGB1 not only acts as a novel "late" inflammatory mediator but is also closely associated with immunosuppression after acute insults. HMGB1 might play an important role in inducing systemic inflammatory response together with host immunological dissonance, resulting in the development of septic complications. Intervention of HMGB1 expression and release presumably provides a potentially effective way to regulate both excessive inflammatory and immune response, thereby as a measure to improve the prognosis of severe sepsis secondary to major trauma.

  17. The effects of high mobility group box-1 protein on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis%重症急性胰腺炎大鼠HMGB1对肠上皮细胞occludin表达的影响

    栾正刚; 郭仁宣


    目的 观察重症急性胰腺炎(SAP)大鼠肠组织中高迁移率族蛋白B1 (HMGB1)表达对肠黏膜上皮细胞紧密连接occludin蛋白表达的影响.方法 逆行胰胆管注射5%牛磺胆酸钠制作SAP模型.健康Wistar大鼠随机(随机数字法)分为对照组、SAP组、二硫代氨基甲酸吡咯烷(PDTC)处理组.测定血淀粉酶(AMY)、内毒素(LPS)及D-乳酸水平;光镜下观察胰腺和肠组织的病理变化;免疫组织化学法观察occludin分布和表达的变化;RT-PCR法检测大鼠肠组织中HMGB1的表达水平;Western blot法检测大鼠肠组织中HMGB1及occludin蛋白的表达水平.采用SPSS 13.0统计分析软件进行处理,P< 0.05为差异具有统计学意义.结果 在建模后24 h,SAP组大鼠血浆LPS及D-乳酸水平明显高于对照组,提示肠屏障通透性明显增加;PDTC处理组大鼠血浆LPS及D-乳酸水平明显低于SAP组(P<0.05).SAP组大鼠肠组织HMGB1表达水平较对照组明显升高,而occludin蛋白的表达较对照组下降;PDTC组大鼠肠组织HMGB1表达水平明显低于SAP组,occludin水平较SAP组升高(P<0.05).结论 SAP时,大鼠肠组织内HMGB1表达升高,通过降低occludin蛋白表达,来增加肠黏膜屏障通透性;PDTC可抑制HMGB1表达,上调occludin蛋白表达,改善肠黏膜屏障通透性.%Objective To observe the effect of high mobility group box-1 protein (HMGB1) on the expression of intestinal epithelial tight junction protein occludin in murine severe acute pancreatitis (SAP).Methods Rat SAP model was estabilished by retrograde injection of 5 % sodium taurocholate into choledochopancreatic duct.Healthy wistar rats were divided randomly (random number) into three groups:control group,SAP group,pyrrolidine dithiocarbamate (PDTC) therapy group.Levels of plasm amylase,lipopolysaccharide (LPS) and D-lactate were determined.The changes of morphological damage of pancreasand intestinal tissues were observed by microscopy.The distribution

  18. Role of high mobility group box-1 on the expression of intestinal epithelial tight junction protein in murine acute necrotizing pancreatitis%HMGB1对急性坏死性胰腺炎大鼠肠上皮细胞紧密连接相关蛋白表达的影响

    栾正刚; 郭仁宣


    目的:观察急性坏死性胰腺炎(ANP)大鼠肠黏膜中高迁移率族蛋白B1 (HMGB1)的表达对肠黏膜上皮细胞紧密连接功能的影响.方法:24只Wistar大鼠随机分为正常对照组、ANP组和丙酮酸乙酯(EP)处理组,分别于建模后24 h取材.测定血浆淀粉酶(AMY)、血浆D-乳酸、肠黏膜髓过氧化物酶(MPO)水平变化;应用Western blot法检测ANP大鼠肠黏膜中HMGB1和occludin蛋白水平的变化.结果:在建模后24 h,大鼠AMY、D-乳酸与肠黏膜MPO水平ANP组明显高于正常对照组和EP处理组(P<0.05),但EP处理组仍高于正常对照组(P< 0.05);ANP组大鼠肠黏膜HMGB1表达水平明显高于正常对照组和EP处理组(P<0.05),EP处理组高于正常对照组(P<0.05);而肠黏膜上皮细胞紧密连接蛋白occludin的表达ANP组较正常对照组和EP处理组下降(P<0.05),EP处理组低于正常对照组(P<0.05).结论:ANP大鼠肠黏膜中HMGB1表达增高,可通过降低occludin蛋白表达,增加肠黏膜屏障通透性.EP能显著抑制HMGB1表达,使occludin蛋白表达升高,对ANP肠黏膜损伤有明显保护作用.%Objective: To investigate the effect of high mobility group box-1 protein (HMGB1) on the expression of intestinal epithelial tight junction protein in murine acute necrotizing pancreatitis(ANP). Methods:Twenty-four male health adult wistar rats were divided randomly into groups: control group, ANP group, and EP treatment group. Specimens were taken at 24h after operation respectively. The concentration of plasma amylase(AMY), plasma D-lactate and the activity of myeloperoxidase(MPO) in the intestinal tissue were determined. The expression of HMGB1 and oc-cludin protein in intestinal mucosa was detected by western blot. Results: In comparison with the control group, levels of plasma D-lactate and MPO in ANP group increased markedly at 24h after operation(P<0.05). The levels of D-lactate and MPO were markedly lowered in EP treatment group 24 h after ANP

  19. Eosinophils Modulate CD4+ T Cell Responses via High Mobility Group Box-1 in the Pathogenesis of Asthma

    Shim, Eun-Jin; Chun, Eunyoung; Lee, Hyun-Seung; Bang, Bo-Ram; Cho, Sang-Heon; Min, Kyung-Up; Park, Heung-Woo


    Eosinophils have been reported to modulate T cell responses. Previously, we reported that high-mobility group box 1 protein (HMGB1) played a key role in the pathogenesis of asthma. This study was conducted to test our hypothesis that eosinophils could modulate T cell responses via HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. We performed in vitro experiments using eosinophils, dendritic cells (DCs), and CD4+ T cells obtained from a murine model of ast...

  20. Detection and identification of tissue specific lectins of the tsetse fly, Glossina tachinoides: Midgut lectin activity with lipopolysaccharide binding specificity

    Lectin that agglutinates human and animal red blood cells (RBCs) was demonstrated in midgut extracts of Glossina tachinoides. The highest haemagglutination titres were against pig and rabbit RBCs. Treatment of rabbit RBCs with pronase, trypsin, neuraminidase, bromelain, glutaraldehyde and periodate reduced the agglutination titres. The lectin is specific for amino, methyl and deoxy derivates of glucose, amino and methyl derivates of mannose, D-galactosamine, N-acetylneuraminic acid and trehalose. In addition, very high reactivity against the lipopolysaccharide of E. coli K 235 was found. Lectin is secreted to the midgut lumen. It consists of a 27 kilodalton protein component that is not glycosylated. Sandwich ELISA permits quantification of lectin in tissue samples. (author). 15 refs, 3 figs, 1 tab

  1. 高迁移率蛋白-1对多发伤后全身炎症反应综合征的预警价值%The relationship between high-mobility group box-1 protein and the prognosis of patients with systemic inflammatory response syndrome after multiple trauma

    唐伦先; 孙志扬


    Objective To observe the relationship between high-mobility group box-1 protein HMGB-1 andthe prognosis of systemic inflammatory response syndrome (SIRS) patients after multiple trauma. Method Sixtypatients with SIRS after multiple trauma in the emergency trauma center were divided into multiple organ dysfunc-tion syndrome (MODS) group and non-MODS group according to the MODS diagnostic criteria, and were followedup for 28 days and then assigned to survival group and fatal group, respectively. Another 20 healthy people wereera-oiled in the conrtol group. The levels of HMGB-1 were measured by ELISA at 24 hours, 3 days, 5 days and 7days after admission. APACHE Ⅱ scores were calculated. Results The concentrations of HMGB- 1 in the patientswith SIRS after trauma at every time point were higher than those in control group (P<0.01). The concentrationsof HMGB-1 and APACHEⅡ scores in the MODS group and the fatal group were higher than those in non-MODSgroup and the survival group (P<0.05 and P<0.01 separately). There was positive correlation between theconcentrations of HMGB-1 and APACHE Ⅱ scores (r=0.7938, P<0.05). Conclusions As an importantpro-inflammatory cytokine in sepsis, HMGB-1 may play a role in the development of SIRS after multiple trauma andcan be used to assess the severity of illness and prognosis.%目的 探讨血清HNGB-1水平对多发伤后全身炎症反应综合征(SIRS)患者病情发生发展的预警价值.方法 将60例入住上海市东方医院急诊创伤中心的多发伤后SIRS患者分为多器官功能障碍综合征组(MODS组)和非MODS组、存活组和死亡组,选择健康体检者20例作为对照组.检测试验组入院24 h、第3、5、7天和对照组血清HMGB-1浓度,并进行APACHE Ⅱ评分.结果 SIRS组入院后HNGB-1浓度进行性上升,各时间点浓度均明显高于对照组(P<0.01);NODS组和死亡组HMGB-1浓度分别明显高于非MODS组和存活组(P<0.05).MODS组的APACHEⅡ评分明显高于非MODS组(P<0

  2. Concentrations of lipopolysaccharide-binding protein, bactericidal/permeability-increasing protein, soluble CD14 and plasma lipids in relation to endotoxaemia in patients with alcoholic liver disease

    Schäfer, C.; Parlesak, Alexandr; Schütt, C.;


    There is increasing evidence that gut leakage in persons with chronic alcohol misuse leads to endotoxaemia, which might contribute to the development of alcoholic hepatitis or cirrhosis. In addition, it was recently shown that the endotoxin-binding capacity of whole blood is reduced in these pati...

  3. 高迁移率族蛋白B1对小鼠调节性T细胞与CD4+CD25-T细胞相互作用的影响%Influence of high mobility group box-1 protein on the correlation between regulatory T cells and CD4+CD25-T cells of spleen in mice

    张莹; 姚咏明; 于燕; 吴瑶; 盛志勇


    Objective To investigate the influence of high mobility group box-1 protein(HMGB1)on the immunosuppression function of splenic regulatory T cells(Tregs)and its potential regulatory mechanism underlying the effect on CD4+CD25-T cells in mice.nethods CD4+CD25+Tregs isolated from the spleens of male BALB/c mice by magnetic beads were seeded on 96-well(1×105 cells/well)cell culture plates coated with 1 μg/ml anti-CD3 and soluble CD28.After being stimulated with HMGB1 for different time and concentrations,the secretions of IL-2 and IL-10 were analyzed by ELISA.Tregs stimulated for 72 hours were cultured with CD4+CD25-T cells together.The suppressive activity of CD4+CD25+Treg to CD4+CD25-T cells was analyzed by MTT test.IL-2,IL-10,IL-4,and interferon(IFN)-γ in the cell suspensions were determined by ELISA.Resuits After stimulation with HMGB1,the suppressive activity of splenic Tregs in mice were significantly down-regulated at 72 hours,when the proportion of Tregs to CD4+CD25-T cells was 1:1.The secretion of IL-2 of Tregs stimulated by HMGB1 was not markedly changed(P>0.05).while a dose-dependent decrease between IL-10 induction and HMGB1 concentration was obviously(P<0.05).When CD4+CD25-T cells were cultured with stimulated Tregs,comparing with unstimulated-Treg group,levels of IL-2 and IFN-γ were elevated following the increased concentration of HMGB1(P<0.05 or P<0.01).Meanwhile the secretion of IL-4 and IL-10 significantly decreased when cultured with stimulated Tregs(P<0.05).Conclusions These data suggested that HMGB1 stimulation can result in significant down-regulation of immunosuppression of splenic Tregs in mice.HMGB1 might be a potential immunoregnlatory signal that influences the proliferation of effector T cells,secretion of IL-2 and cells-polarization by inhibiting CD4+CD25+Tregs activity.%目的 观察高迁移率族蛋白B1(HMGB1)对调节性T细胞(Treg)与CD4+CD25-T细胞相互作用的影响,并初步探讨其影

  4. Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

    Xiaoao Pang


    Full Text Available We investigated the significance of high- mobility group box1 (HMGB1 and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3, IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN, and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05. In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05. HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05. HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05. Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.

  5. Four jointed box 1 promotes angiogenesis and is associated with poor patient survival in colorectal carcinoma.

    Nicole T Al-Greene

    Full Text Available Angiogenesis, the recruitment and re-configuration of pre-existing vasculature, is essential for tumor growth and metastasis. Increased tumor vascularization often correlates with poor patient outcomes in a broad spectrum of carcinomas. We identified four jointed box 1 (FJX1 as a candidate regulator of tumor angiogenesis in colorectal cancer. FJX1 mRNA and protein are upregulated in human colorectal tumor epithelium as compared with normal epithelium and colorectal adenomas, and high expression of FJX1 is associated with poor patient prognosis. FJX1 mRNA expression in colorectal cancer tissues is significantly correlated with changes in known angiogenesis genes. Augmented expression of FJX1 in colon cancer cells promotes growth of xenografts in athymic mice and is associated with increased tumor cell proliferation and vascularization. Furthermore, FJX1 null mice develop significantly fewer colonic polyps than wild-type littermates after combined dextran sodium sulfate (DSS and azoxymethane (AOM treatment. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. Taken together our results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.

  6. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F


    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  7. High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma

    Xu, Yun-Fei; Ge, Fu-Jun; Han, Bo; Yang, Xiao-Qing; Su, Hong; Zhao, An-Cheng; Zhao, Ming-Hong; Yang, Yu-Bao; Yang, Jie


    AIM: To evaluate the prognostic value of high-mobility group box 1 (HMGB1) expression in intrahepatic cholangiocarcinoma (IHCC) and the possible underlying mechanism. METHODS: Tissue microarray was constructed from 65 IHCC patients. Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C (VEGF-C). Real-time PCR and Western blot analyses were used to study transcript and protein levels. The interaction between HMGB1 and VEGF-C was evaluated by siRNA, real-time PCR, and enzyme-linked immuno assays. The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed by χ2 test, and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Cox-regression model, respectively. RESULTS: Overall, overexpression of HMGB1 was found in 38/65 (58.8%) IHCCs, whereas VEGF-C overexpression was present in 30/65 (46.2%) cases. Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density (P = 0.031, r = 0.268) and VEGF-C expression (P = 0.041, r = 0.254). With univariate analysis, both HMGB1 (P = 0.001) and VEGF-C (P = 0.004) were identified to be significantly associated with overall survival rate. Multivariate analysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs (P = 0.005). siRNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelial-mesenchymal transition (EMT) by elevating E-Cadherin expression and reducing expression of N-Cadherin, Vimentin and Snail in RBE cells. Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C, whereas the recombinant HMGB1 increased the VEGF-C level in RBE cells (both P < 0.05), which suggested that HMGB1 could promote lymphatic microvessel density, and subsequently lymphatic invasion, via promoting VEGF-C expression. CONCLUSION: Our results define an important role of HMGB1 in the progression of

  8. Adsorption of the Inflammatory Mediator High-Mobility Group Box 1 by Polymers with Different Charge and Porosity

    Carla Tripisciano


    Full Text Available High-mobility group box 1 protein (HMGB1 is a conserved protein with a variety of biological functions inside as well as outside the cell. When released by activated immune cells, it acts as a proinflammatory cytokine. Its delayed release has sparked the interest in HMGB1 as a potential therapeutic target. Here, we studied the adsorption of HMGB1 to anionic methacrylate-based polymers as well as to neutral polystyrene-divinylbenzene copolymers. Both groups of adsorbents exhibited efficient binding of recombinant HMGB1 and of HMGB1 derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells. The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself (e.g., acetylation, phosphorylation, and oxidation, interaction with other plasma proteins or anticoagulants (e.g., heparin, or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity.

  9. Purpurogallin, a Natural Phenol, Attenuates High-Mobility Group Box 1 in Subarachnoid Hemorrhage Induced Vasospasm in a Rat Model

    Chih-Zen Chang


    Full Text Available High-mobility group box 1 (HMGB1 was shown to be an important extracellular mediator involved in vascular inflammation of animals following subarachnoid hemorrhage (SAH. This study is of interest to examine the efficacy of purpurogallin, a natural phenol, on the alternation of cytokines and HMGB1 in a SAH model. A rodent double hemorrhage SAH model was employed. Basilar arteries (BAs were harvested to examine HMGB1 mRNA and protein expression (Western blot. CSF samples were to examine IL-1β, IL-6, IL-8, and TNF-α (rt-PCR. Deformed endothelial wall, tortuous elastic lamina, and necrotic smooth muscle were observed in the vessels of SAH groups but were absent in the purpurogallin group. IL-1β, IL-6, and TNF-α in the SAH only and SAH plus vehicle groups were significantly elevated (P<0.01. Purpurgallin dose-dependently reduced HMGB1 protein expression. Likewise, high dose purpurogallin reduced TNF-α and HMGB1 mRNA levels. In conclusion, purpurogallin exerts its neuroinflammation effect through the dual effect of inhibiting IL-6 and TNF-α mRNA expression and reducing HMGB1 protein and mRNA expression. This study supports purpurogallin could attenuate both proinflammatory cytokines and late-onset inflammasome in SAH induced vasospasm.

  10. Effects of Ethyl Pyruvate on High Mobility Group Box1 gene expression in septic lung of rat

    Lian Zeng; Shanglong Yao; Dong Liu; Yuelan Wang


    Objective: Ethyl Pyruvate (EP) has been shown to be an effective anti-inflammatory agent in a variety of model systems. The aim of this study was to investigate the effects of EP on High Mobility Group Box1 (HMGB1) genes expression and the possible mechanisms of EP protecting against acute lung injury induced by sepsis. Methods: Forty Wistar rats were randomly divided into normal controls, sham operation, acute lung injury, and EP treatment (40 mg/kg intra-peritoneally every 6 hrs ) groups. At the time points of 24 hours the animals in each group were sacrificed, and the lungs were harvested. Wet/dry lung weight ratio, the protein in the bronchoalveolar lavage fluid(BALF), and pulmonary permeability index(PPI) were determined. The histological morphology of lung was observed under microscope. The expression of HMGB1 mRNA was measured using semi-quantitative RT-PCR. Results: EP treatment decreased wet/dry lung weight ratio, the protein in the BALF, and PPI ( P < 0.01 ). The histological morphology of lung injury was ameliorated. EP significantly inhibited the HMGB1 mRNA expression (P < 0.01 ). HMGB1 mRNA expression in lungs positivelycorrelation with wet/dry lung weight ratio, the protein in the BALF, and PPI. Conclusion: EP administered inhibits HMGB1 mRNAexpression, and protects the lungs against acute injury induced by sepsis.

  11. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  12. Pivotal role of high-mobility group box 1 (HMGB1) signaling pathways in glioma development and progression.

    Angelopoulou, Efthalia; Piperi, Christina; Adamopoulos, Christos; Papavassiliou, Athanasios G


    Human gliomas represent the most common type of intracranial tumors, with highest morbidity and mortality. They are characterized by excessive invasiveness and cell proliferation while their unclear boundaries predispose to tumor recurrence soon after conventional treatment. Elucidation of the molecular mechanisms implicated in their development and/or treatment resistance is highly demanded. The high-mobility group box 1 (HMGB1) protein, a highly conserved nuclear protein that functions as a chromatin-binding factor, facilitating nucleosome stabilization and regulating gene transcription, has been implicated in glioma formation and progression. Extracellular released HMGB1 binds to high-affinity receptors, including the receptor for advanced glycation end-products (RAGE) and toll-like receptor (TLR)-2, TLR-4, and TLR-9. Upon receptor binding, HMGB1 triggers the activation of key signaling pathways and immune responses, involved in the regulation of cell growth, differentiation, motility, and apoptosis. Based on the type of receptor and/or cell, HMGB1 is capable to promote oncogenesis or suppress tumor growth, thus affecting treatment efficacy. Herein, we discuss recent evidence implicating HMGB1 in glioma cell differentiation, proliferation, and metastasis with both clinical and prognostic significance. In addition, potential therapeutic approaches to target this protein in order to reduce chemoresistance of glioma cells are also addressed. PMID:27262996

  13. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Zhang, Xufang, E-mail: [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)


    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  14. Plasma high-mobility group box 1 levels predict mortality after ST-segment elevation myocardial infarction

    Sørensen, Morten V; Pedersen, Sune; Møgelvang, Rasmus;


    We evaluated the potential association between plasma high-mobility group box 1 (HMGB1) levels and outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention....

  15. Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

    Salunya Tancharoen


    Full Text Available High mobility group box 1 (HMGB1, a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE, which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia lipopolysaccharide (LPS on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1. RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-κB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection.

  16. Poly(ADP-ribose) polymerase activation induces high mobility group box 1 release from proximal tubular cells during cisplatin nephrotoxicity.

    Kim, J


    Cisplatin is one of the most potent chemotherapy drugs against cancer, but its major side effect such as nephrotoxicity limits its use. Inhibition of poly(ADP-ribose) polymerase (PARP) protects against various renal diseases via gene transactivation and/or ADP-ribosylation. However, the role of PARP in necrotic cell death during cisplatin nephrotoxicity remains an open question. Here we demonstrated that pharmacological inhibition of PARP by postconditioning dose-dependently prevented tubular injury and renal dysfunction following cisplatin administration in mice. PARP inhibition by postconditioning also attenuated ATP depletion during cisplatin nephrotoxicity. Systemic release of high mobility group box 1 (HMGB1) protein in plasma induced by cisplatin administration was significantly diminished by PARP inhibition by postconditioning. In in vitro kidney proximal tubular cell lines, PARP inhibition by postconditioning also diminished HMGB1 release from cells. These data demonstrate that cisplatin-induced PARP1 activation contributes to HMGB1 release from kidney proximal tubular cells, resulting in the promotion of inflammation during cisplatin nephrotoxicity. PMID:26447520

  17. High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina

    Ahmed M. Abu El-Asrar


    Full Text Available To test the hypothesis that brain-derived neurotrophic factor-(BDNF- mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1 in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE, soluble intercellular adhesion molecule-1 (sICAM-1, monocyte chemoattractant protein-1 (MCP-1, and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.

  18. Downregulation of high mobility group box 1 modulates telomere homeostasis and increases the radiosensitivity of human breast cancer cells.

    Ke, Shaobo; Zhou, Fuxiang; Yang, Hui; Wei, Yuehua; Gong, Jun; Mei, Zijie; Wu, Lin; Yu, Haijun; Zhou, Yunfeng


    The functions of the high mobility group box 1 (HMGB1) in tumor cells include replenishing telomeric DNA and maintaining cell immortality. There is a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Our aim was to elucidate the relationship among HMGB1, telomere homeostasis and radiosensitivity in MCF-7 cells. In this study, we established stably transfected control (MCF-7-NC) and HMGB1 knockdown (MCF-7-shHMGB1) cell lines. The expression of HMGB1 mRNA and the relative telomere length were examined by real-time PCR. Radiosensitivity was detected by clonogenic assay. The protein expressions were determined by western blot analysis. The telomerase activity was detected by PCR-ELISA. Proliferation ability was examined by CCK-8 assay. Cell cycle and apoptosis were examined by flow cytometry. DNA damage foci were detected by immunofluorescence. ShRNA-mediated downregulation of HMGB1 expression increased the radiosensitivity of MCF-7 cells, and reduced the accumulation of hTERT and cyclin D1. Moreover, knockdown of HMGB1 in MCF-7 cells inhibited telomerase activity and cell proliferation, while increasing the extent of apoptosis. Downregulation of HMGB1 modulated telomere homeostasis by changing the level of telomere-binding proteins, such as TPP1 (PTOP), TRF1 and TRF2. This downregulation also inhibited the ATM and ATR signaling pathways. The current data demonstrate that knockdown of HMGB1 breaks telomere homeostasis, enhances radiosensitivity, and suppresses the repair of DNA damage in human breast cancer cells. These results suggested that HMGB1 might be a potential radiotherapy target in human breast cancer. PMID:25501936

  19. Spinal high-mobility group box 1 contributes to mechanical allodynia in a rat model of bone cancer pain

    Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response.

  20. Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages


    Lipopolysaccharide binding protein (LBP) is an acute-phase reactant that binds bacterial LPS. We show that LBP binds to the surface of live Salmonella and to LPS coated erythrocytes (ELPS), and strongly enhances the attachment of these particles to macrophages. LBP bridges LPS- coated particles to macrophages (MO) by first binding to the LPS, then binding to MO. Pretreatment of ELPS with LBP enabled binding to MO, but pretreatment of MO had no effect. Moreover, MO did not recognize erythrocyt...

  1. Inhibition of high-mobility group box 1 as therapeutic option in autoimmune disease : lessons from animal models

    Schaper, Fleur; Heeringa, Peter; Bijl, Marc; Westra, Johanna


    Purpose of review High-mobility group box 1 (HMGB1) is a molecule that has gained much attention in the last couple of years as an important player in innate immune responses and modulating factor in several (auto) immune diseases. Furthermore, advancements have been made in identifying the diverse

  2. The high-mobility group box 1 cytokine induces transporter-mediated release of glutamate from glial subcellular particles (gliosomes) prepared from in situ-matured astrocytes.

    Bonanno, Giambattista; Raiteri, Luca; Milanese, Marco; Zappettini, Simona; Melloni, Edon; Pedrazzi, Marco; Passalacqua, Mario; Tacchetti, Carlo; Usai, Cesare; Sparatore, Bianca


    The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and beta-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-alphaM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several approximately 30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca(2+) and Ca(2+) release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [(3)H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca(2+) concentration, but it was blocked by dl-threo-beta-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine

  3. The role of High Mobility Group Box 1 (HMGB1) in colorectal cancer

    Süren, Dinç; Yıldırım, Mustafa; Demirpençe, Özlem; Kaya, Vildan; Alikanoğlu, Arsenal Sezgin; Bülbüller, Nurullah; Yıldız, Mustafa; Sezer, Cem


    Background HMGB1, the most important member of the high mobility group box protein family, is a nuclear protein with different functions in the cell; it has a role in cancer progression, angiogenesis, invasion, and metastasis development. We studied the expression of HMGB1 and whether it is a prognostic factor in colorectal carcinoma. Material/Methods The study included 110 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical res...

  4. The Effect of a Novel Cytokine, High Mobility Group Box 1 Protein, on the Development of Traumatic Sepsis

    YAO Yong-ming; SHENG Zhi-yong; HUANG Li-feng


    @@ Sepsis and subsequent multiple organ dysfunction syndrome (MODS) are frequent complications after severe traumata or burns involving a large area, and these remain as the two most common causes of morbidity and mortality in critical illnesses. Despite the recent rapid advances in intensive care technologies and the use of costly treatments with new antibiotics, the mortality in patients with severe sepsis still reaches as high as 40% to 50% in many countries.

  5. High-mobility group box-1 release into fetal circulation from umbilical cord tissue and amniotic epithelium in fetal ischemia.

    Nakamura, Toshihiko; Yoshioka, Toshirou; Yamada, Shingo; Miyasho, Taku; Sakakibara, Nana; Hatanaka, Daishuke


    We report the case of a baby with low birthweight born by emergency caesarean section at 33 weeks 2 days' gestation due to placental abruption. High-mobility group box-1 (HMGB-1) and interleukin-17 concentration in the umbilical cord blood were high at 55.7 ng/mL and 50.7 pg/mL, respectively. On immunostaining of umbilical cord and amniotic epithelium, HMGB-1 was identified in the nuclei of vascular endothelial cells and cytoplasm of the surrounding cells in the umbilical cord. This suggests that, in the present case of placental abruption and subsequent ischemic placenta and fetus, the high level of HMGB-1 observed was due to the release of HMGB-1 into the umbilical cord blood from the vascular endothelial cells of the umbilical cord. PMID:27097754

  6. Severity of sepsisis is correlated with the elevation of serum high-mobility group box 1 in rats

    HOU Li-chao; XIONG Li-ze; QIN Ming-zhe; ZHENG Li-na; LU Yan; WANG Qiang; PENG Dao-rong; YU Xin-ping; XIN Yu-chang; JI Gen-lin


    Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine,high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats.Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed.Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin Ⅰ, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney.Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.

  7. Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

    Wang, Y.F. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China); Wu, M. [Department of Surgery, Jinshan Pavilion Forest Hospital, Shanghai (China); Ma, B.J.; Cai, D.A.; Yin, B.B. [Department of Surgery, Huashan Hospital, Fudan University, Shanghai (China)


    In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

  8. Serum high mobility group box-1 (HMGB1 is closely associated with the clinical and pathologic features of gastric cancer

    Chung Jae


    Full Text Available Abstract Background High mobility group box-1 (HMGB1 is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. Methods A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA method. Clinical parameters, International Union Against Cancer (UICC TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. Results The serum HMGB1 levels were significantly different among disease groups (ANOVA, p and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p . However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05. The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA (30–40% of sensitivity. Conclusion HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.

  9. Changes of High Mobility Group box 1 in Serum of Pig Acute Hepatic Failure Model and Significance

    Fan ZHANG; Yongwen HE; Zhongping DUAN


    The role of the high mobility group box 1 (HMGB-1) in acute hepatic failure and the ef- fect of artificial liver support system treatment on HMGB-1 level were investigated. Pig models of acute hepatic failure were induced by D-galactosamine and randomly divided into two groups with or without artificial liver support system treatment. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were detected by the enzyme linked immunosorbent assay (ELISA), the expression of HMGB-1 by Western blot, and serum levels of HMGB-1, liver function and hepatic pathology were observed after artificial liver support system treatment. The levels of TNF-α and IL-1β were increased and reached the peak at 24th h in the acute hepatic failure group, then quickly decreased. The serum level of HMGB-1 was increased at 24th h in the acute hepatic failure group and reached the peak at 48th h, then kept a stable high level. Significant liver injury appeared at 24th h and was continuously getting worse in the pig models of acute hepatic failure. In contrast, the liver injury was significantly alleviated and serum level of HMGB-1 was significantly decreased in the group treated with artificial liver support system (P<0.05). It was suggested that HMGB-1 may participate in the inflammatory response and liver injury in the late stage of the acute liver failure. Artificial liver support system treatment can reduce serum HMGB-1 level and relieve liver pathological damage.

  10. Toll-like receptor 4 and high-mobility group box 1 are critical mediators of tissue injury and survival in a mouse model for heatstroke.

    Mohammed Dehbi

    Full Text Available The molecular mechanisms that initiate the inflammatory response in heatstroke and their relation with tissue injury and lethality are not fully elucidated. We examined whether endogenous ligands released by damaged/stressed cells such as high-mobility group box 1 (HMGB1 signaling through Toll-like receptor 4 (TLR4 may play a pathogenic role in heatstroke. Mutant TLR4-defective (C3H/HeJ and wild type (C3H/HeOuJ mice were subjected to heat stress in an environmental chamber pre-warmed at 43.5 °C until their core temperature reached 42.7°C, which was taken as the onset of heatstroke. The animals were then allowed to recover passively at ambient temperature. A sham-heated group served as a control. Mutant mice displayed more histological liver damage and higher mortality compared with wild type mice (73% vs. 27%, respectively, P<0.001. Compared to wild type mice, mutant mice exhibited earlier plasma release of markers of systemic inflammation such as HMGB1 (206 ± 105 vs. 63 ± 21 ng/ml; P = 0.0018 and 209 ± 100 vs. 46 ± 32 ng/ml; P<0.0001, IL-6 (144 ± 40 vs. 46 ± 20 pg/ml; P<0.001 and 184 ± 21 vs. 84 ± 54 pg/ml; P = 0.04, and IL-1β (27 ± 4 vs. 1.7 ± 2.3 pg/ml; P<0.0001 at 1 hour. Both strains of mice displayed early release of HMGB1 into the circulation upstream of IL-1β and IL-6 responses which remained elevated up to 24 h. Specific inhibition of HMGB1 activity with DNA-binding A Box (600 µg/mouse protected the mutant mice against the lethal effect of heat stress (60% A Box vs. 18% GST protein, P = 0.04. These findings suggest a protective role for the TLR4 in the host response to severe heat stress. They also suggest that HMGB1 is an early mediator of inflammation, tissue injury and lethality in heatstroke in the presence of defective TLR4 signaling.

  11. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    Good, David W; George, Thampi; Watts, Bruns A


    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  12. Mutations in PurBox1 of the Bacillus subtilis pur operon control site affect adenine-regulated expression in vivo

    XUAN Jinsong; Howard Zalkin; WENG Manli


    Transcription of the Bacillus subtilis pur operon is regulated by a purine repressor (PurR)-DNA control site interaction. The pur operon control site has two PurBoxes that are required for high-affinity PurR binding. An upstream, strong-binding PurBox1 is at position -81 to -68 relative to the transcription start site and a downstream weak-binding PurBox2 is at position -49 to -36. We constructed three PurBox1 mutations and the effects on binding of PurR to the control region in vitro and on regulation of pur operon expression in vivo were investigated. The mutations significantly reduced the binding of PurR to control region DNA. In strains with G-75A, G-75T and a five bp deletion (△5) pur operon repression was defective in vivo. In addition in vivo PurR titration was used to confirm that sequences flanking PurBox1 and PurBox2 are required for PurR binding to the pur operon control site.

  13. Apolipophorin III: lipopolysaccharide binding requires helix bundle opening

    Leon, Leonardo J.; Idangodage, Hasitha; Wan, Chung-Ping L.; Weers, Paul M.M.


    Apolipophorin III (apoLp-III) is a prototypical apolipoprotein used for structure-function studies. Besides its crucial role in lipid transport, apoLp-III is able to associate with fungal and bacterial membranes and stimulate cellular immune responses. We recently demonstrated binding interaction of apoLp-III of the greater wax moth, Galleria mellonella, with lipopolysaccharides (LPS). In the present study, the requirement of helix bundle opening for LPS binding interaction was investigated. ...

  14. 蜂毒素对人肝癌细胞中HMGB1及VEGF-C表达的影响%Effect of melittin on high mobility group box 1 and vascular endothelial growth factors C expressions in hepatocarcinoma cells

    曹清心; 汪晨; 刘宇; 赵丹; 凌昌全


    目的 观察蜂毒素对人肝癌细胞株HepG2中高迁移率族蛋白B1(high mobility group box 1,HMGB1)及血管内皮生长因子C(vascular endothelial growth factors C,VEGF-C)表达的影响,探讨其抑制肝癌细胞的作用机制.方法 肝癌细胞HepG2体外培养,经蜂毒素处理后,采用四甲基偶氮唑蓝(MTT)法了解蜂毒素对肝癌细胞增殖的影响,用Western-blotting、qRT-PCR方法检测HMGB1、VEGF-C的表达.结果 蜂毒素在体外能够抑制肝癌细胞的增殖活性;Westem-blotting结果显示,蜂毒素可抑制 HMGB1的表达,且呈浓度依赖性,但对VEGF-C的蛋白表达无明显影响;qRT-PCR结果显示,蜂毒素在mRNA水平均具有抑制HMGB1、VEGF-C表达的作用.结论 蜂毒素可降低肝癌细胞的增殖活性,并可能通过HMGB1、VEGF-C的表达发挥抗肝癌作用.%Objective To observe the effect of melittin on the expressions of high mobility group box 1 (HMGB1) and vascular endothelial growth factors C( VEGF-C) in hepatocarcinoma cells in vitro and to study the mechanisms of melittin in hepatocarcinoma cells. Methods HepG2 cell line was treated with melittin in vitro. The inhibition of proliferation was delected by MTT assay. The expressions of HMGB1 and VEGF-C were detected by western-blotting and real-time quantitative PCR{ qRT-PCR) assay. Results Melittin inhibited cell proliferation in vitro. Western-blotting outcome showed that melitlin could down-regulate the protein of HMGB1, while VEGF-C expression did not change. qRT-PCR results showed that HMGBI and VEGF-C mRNA expressions were down-regulate by melittin. Conclusion It is suggested that melittin can inhibit hepatocarcinoma cells proliferation. The effect of melittin in inducing anti-hepatocarcinoma may be related with down-regulation of HMGBI and VEGF-C.

  15. Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models.

    Song, Ji Hyun; Kim, Ji Yeon; Piao, Chunxian; Lee, Seonyeong; Kim, Bora; Song, Su Jeong; Choi, Joon Sig; Lee, Minhyung


    In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI. PMID:27196743

  16. PLUNC is a novel airway surfactant protein with anti-biofilm activity.

    Lokesh Gakhar

    Full Text Available BACKGROUND: The PLUNC ("Palate, lung, nasal epithelium clone" protein is an abundant secretory product of epithelia present throughout the conducting airways of humans and other mammals, which is evolutionarily related to the lipid transfer/lipopolysaccharide binding protein (LT/LBP family. Two members of this family--the bactericidal/permeability increasing protein (BPI and the lipopolysaccharide binding protein (LBP--are innate immune molecules with recognized roles in sensing and responding to Gram negative bacteria, leading many to propose that PLUNC may play a host defense role in the human airways. METHODOLOGY/PRINCIPAL FINDINGS: Based on its marked hydrophobicity, we hypothesized that PLUNC may be an airway surfactant. We found that purified recombinant human PLUNC greatly enhanced the ability of aqueous solutions to spread on a hydrophobic surface. Furthermore, we discovered that PLUNC significantly reduced surface tension at the air-liquid interface in aqueous solutions, indicating novel and biologically relevant surfactant properties. Of note, surface tensions achieved by adding PLUNC to solutions are very similar to measurements of the surface tension in tracheobronchial secretions from humans and animal models. Because surfactants of microbial origin can disperse matrix-encased bacterial clusters known as biofilms [1], we hypothesized that PLUNC may also have anti-biofilm activity. We found that, at a physiologically relevant concentration, PLUNC inhibited biofilm formation by the airway pathogen Pseudomonas aeruginosa in an in vitro model. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the PLUNC protein contributes to the surfactant properties of airway secretions, and that this activity may interfere with biofilm formation by an airway pathogen.

  17. In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin.

    Santoro, Matteo; Maetzler, Walter; Stathakos, Petros; Martin, Heather L; Hobert, Markus A; Rattay, Tim W; Gasser, Thomas; Forrester, John V; Berg, Daniela; Tracey, Kevin J; Riedel, Gernot; Teismann, Peter


    High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells - including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression. Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner. These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD. PMID:26921471

  18. Mucosal immunization with high-mobility group box 1 in chitosan enhances DNA vaccine-induced protection against coxsackievirus B3-induced myocarditis.

    Wang, Maowei; Yue, Yan; Dong, Chunsheng; Li, Xiaoyun; Xu, Wei; Xiong, Sidong


    Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the Picornaviridae family. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis. PMID:24027262

  19. Plasma concentration of high-mobility group box 1 (HMGB1) after 100 drop to vertical jumps and after a 1200-km bicycle race.

    Behringer, M; Kilian, Y; Montag, J; Geesmann, B; Mester, J


    High-mobility group box 1 (HMGB1) has recently been reported to be involved in proinflammation and tissue repair. Therefore, we hypothesized that HMGB1 is released into the bloodstream after eccentric exercises or prolonged endurance activities. Blood samples from 11 participants that performed 100 drop to vertical jumps (DVJ) and from 10 participants that took part in the 1200-km 'Paris-Brest-Paris' bicycle race (PBP) were tested for HMGB1 and creatine kinase (CK) levels. CK increased after both DVJ (pre: 150.6 ± 81.5 U/L; post: 188.8 ± 95.5 U/L 8 h: 790.5 ± 346.4 U/L) and PBP (pre: 81.3 ± 36.4 U/L; post: 725.2 ± 229.5 U/L; 12 h: 535.8 ± 188.6 U/L), indicating membrane damage. However, HMGB1 plasma levels remained below the detection limit (78 pg/mL) of the applied enzyme-linked immunosorbent assay kit for all blood samples analysed. That is, neither high intensity eccentric exercises (DVJ) nor prolonged endurance events (PBP) seemed to affect HMGB1 levels in blood at selected time points. PMID:26880688

  20. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1 Signaling Pathway in Streptozotocin-Induced Diabetic Rats

    Eunjin Sohn


    Full Text Available High-mobility group box-1 (HMGB1 is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE and the activity of nuclear factor-kappa B (NF-κB in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.

  1. Ovocalyxin-36 is a pattern recognition protein in chicken eggshell membranes.

    Cordeiro, Cristianne M M; Esmaili, Hamed; Ansah, George; Hincke, Maxwell T


    The avian eggshell membranes are essential elements in the fabrication of the calcified shell as a defense against bacterial penetration. Ovocalyxin-36 (OCX-36) is an abundant avian eggshell membrane protein, which shares protein sequence homology to bactericidal permeability-increasing protein (BPI), lipopolysaccharide-binding protein (LBP) and palate, lung and nasal epithelium clone (PLUNC) proteins. We have developed an efficient method to extract OCX-36 from chicken eggshell membranes for purification with cation and anion exchange chromatographies. Purified OCX-36 protein exhibited lipopolysaccharide (LPS) binding activity and bound lipopolysaccharide (LPS) from Escherichia coli O111:B4 in a dose-dependent manner. OCX-36 showed inhibitory activity against growth of Staphylococcus aureus ATCC 6538. OCX-36 single nucleotide polymorphisms (SNPs) were verified at cDNA 211 position and the corresponding proteins proline-71 (Pro-71) or serine-71 (Ser-71) were purified from eggs collected from genotyped hens. A significant difference between Pro-71 and Ser-71 OCX-36 for S. aureus lipoteichoic acid (LTA) binding activity was detected. The current study is a starting point to understand the innate immune role that OCX-36 may play in protection against bacterial invasion of both embryonated eggs (relevant to avian reproductive success) and unfertilized table eggs (relevant to food safety). PMID:24391897

  2. PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

    Tamai, Katsuto; Yamazaki, Takehiko; Chino, Takenao; Ishii, Masaru; Otsuru, Satoru; Kikuchi, Yasushi; Iinuma, Shin; Saga, Kotaro; Nimura, Keisuke; Shimbo, Takashi; Umegaki, Noriko; Katayama, Ichiro; Miyazaki, Jun-ichi; Takeda, Junji; McGrath, John A.


    The role of bone marrow cells in repairing ectodermal tissue, such as skin epidermis, is not clear. To explore this process further, this study examined a particular form of cutaneous repair, skin grafting. Grafting of full thickness wild-type mouse skin onto mice that had received a green fluorescent protein-bone marrow transplant after whole body irradiation led to an abundance of bone marrow-derived epithelial cells in follicular and interfollicular epidermis that persisted for at least 5 ...

  3. Endotoxin-binding proteins in nasal lavage: evaluation as biomarkers to occupational endotoxin exposure.

    Borm, P J; Jetten, M; Keman, S; Schins, R P


    Exposure to endotoxin (LPS) can cause chronic respiratory disease, with symptoms that are more pronounced after exposure-free periods. The aim of this study was to evaluate LPS-response modulating proteins in nasal lavage and plasma as biomarkers for exposure to airborne endotoxin. We applied nasal lavage, lung function and exposure measurements in a small group (n = 11) of cotton workers during 6 weeks of observation (after 2 weeks free from exposure) and ten external controls. Lipopolysaccharide binding protein (LBP) and bactericidal/permeability increasing protein (BPI) were measured in nasal lavage fluid (NALF) along with classic markers such as differential cell counts, Interleukin-8 (IL-8) and albumin, to evaluate their use as markers in endotoxin exposure. In all control subjects and cotton workers LBP and BPI were readily detectable in NALF, although a high intra- and intervariability was noted. At the exposure levels in this study (cotton dust, geometric mean (GM) = 1.10 mg m(-3); endotoxin, GM = 2869 EU m(-3)), plasma BPI and BPI and LBP in NALF were significantly (P measurement period a significant increase was noted in BPI, albumin and BPI/LBP ratio in NALF (P endotoxin or dust exposure measurements. The data show that LBP and BPI are present in nasal lavage fluid and that these markers as well as their ratio increase during airborne endotoxin exposure in cotton workers. PMID:23885948

  4. Biophysical characterization of the interaction of Limulus polyphemus endotoxin neutralizing protein with lipopolysaccharide.

    Andrä, Jörg; Garidel, Patrick; Majerle, Andreja; Jerala, Roman; Ridge, Richard; Paus, Erik; Novitsky, Tom; Koch, Michel H J; Brandenburg, Klaus


    Endotoxin-neutralizing protein (ENP) of the horseshoe crab is one of the most potent neutralizers of endotoxins [bacterial lipopolysaccharide (LPS)]. Here, we report on the interaction of LPS with recombinant ENP using a variety of physical and biological techniques. In biological assays (Limulus amebocyte lysate and tumour necrosis factor-alpha induction in human mononuclear cells), ENP causes a strong reduction of the immunostimulatory ability of LPS in a dose-dependent manner. Concomitantly, the accessible negative surface charges of LPS and lipid A (zeta potential) are neutralized and even converted into positive values. The gel to liquid crystalline phase transitions of LPS and lipid A shift to higher temperatures indicative of a rigidification of the acyl chains, however, the only slight enhancement of the transition enthalpy indicates that the hydrophobic moiety is not strongly disturbed. The aggregate structure of lipid A is converted from a cubic into a multilamellar phase upon ENP binding, whereas the secondary structure of ENP does not change due to the interaction with LPS. ENP contains a hydrophobic binding site to which the dye 1-anilino-8-sulfonic acid binds at a K(d) of 19 micro m, which is displaced by LPS. Because lipopolysaccharide-binding protein (LBP) is not able to bind to LPS when ENP and LPS are preincubated, tight binding of ENP to LPS can be deduced with a K(d) in the low nonomolar range. Importantly, ENP is able to incorporate by itself into target phospholipid liposomes, and is also able to mediate the intercalation of LPS into the liposomes thus acting as a transport protein in a manner similar to LBP. Thus, LPS-ENP complexes might enter target membranes of immunocompetent cells, but are not able to activate due to the ability of ENP to change LPS aggregates from an active into an inactive form. PMID:15128313

  5. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport.

    Alva, Vikram; Lupas, Andrei N


    The tubular lipid-binding (TULIP) superfamily has emerged in recent years as a major mediator of lipid sensing and transport in eukaryotes. It currently encompasses three protein families, SMP-like, BPI-like, and Takeout-like, which share a common fold. This fold consists of a long helix wrapped in a highly curved anti-parallel β-sheet, enclosing a central, lipophilic cavity. The SMP-like proteins, which include subunits of the ERMES complex and the extended synaptotagmins (E-Syts), appear to be mainly located at membrane contacts sites (MCSs) between organelles, mediating inter-organelle lipid exchange. The BPI-like proteins, which include the bactericidal/permeability-increasing protein (BPI), the LPS (lipopolysaccharide)-binding protein (LBP), the cholesteryl ester transfer protein (CETP), and the phospholipid transfer protein (PLTP), are either involved in innate immunity against bacteria through their ability to sense lipopolysaccharides, as is the case for BPI and LBP, or in lipid exchange between lipoprotein particles, as is the case for CETP and PLTP. The Takeout-like proteins, which are comprised of insect juvenile hormone-binding proteins and arthropod allergens, transport, where known, lipid hormones to target tissues during insect development. In all cases, the activity of these proteins is underpinned by their ability to bind large, hydrophobic ligands in their central cavity and segregate them away from the aqueous environment. Furthermore, where they are involved in lipid exchange, recent structural studies have highlighted their ability to establish lipophilic, tubular channels, either between organelles in the case of SMP domains or between lipoprotein particles in the case of CETP. Here, we review the current knowledge on the structure, versatile functions, and evolution of the TULIP superfamily. We propose a deep evolutionary split in this superfamily, predating the Last Eukaryotic Common Ancestor, between the SMP-like proteins, which act on

  6. 外源性一氧化碳释放分子对脓毒症大鼠肺组织高迁移率族蛋白B1表达的影响%Effect of extrinsic carbon monoxide releasing-molecule-2 on the expression of high mobility group box 1 in rats with sepsis-induced lung injury

    徐丽; 鲍红光; 张勇; 刘晨辉; 张蕊


    Objective To investigate the effect of extrinsic carbon monoxide releasing-molecule-2 (CORM-2) on the expression of high mobility group box 1 (HMGB1) in rats with sepsis-induced lung injury.Methods The animal model of sepsis was established by ceal ligation and puncture (CLP) in 150 Wistar male rats,which were randomly divided into 3 groups:C group,CLP group and CORM-2 group.At 6,12,24,48,72 h,HMGB1 concentration in lung homogenate was detected by ELISA.Lung HMGB1 mRNA was detected with real-time fluorescent quantitative polymerase chain reaction (real-time RT-PCR),DNA-binding activity of STAT3 was analyzed by electrophoretic mobility shift assay (EMSA).Malonaldehyde (MDA) content in lung tissue and the wet-to-dry (W/D) weight ratio of lung tissue were determined.The extent of cell apoptosis was determined by flow cytometry.Results Compared with C group,gene and protein expression of HMGB1 in groups CLP,CORM-2 were increased,DNA-binding activity of STAT3 and MDA content in lung homogenate were raise,as well as the rates of apoptosis and lung W/D weight ratio.Compared with CLP group,gene and protein expression of HMGB1 in group CORM-2 was decreased,DNA-binding activity of STAT3 and MDA content in lung homogenate were lower,as well as the rates of apoptosis and lung W/D weight ratio.Conclusions CORM-2 intervention may down-regnlate HMGB 1 expression and attenuate lung injury in CLP-induced septic rats.%目的 研究外源性一氧化碳释放分子(CORM-2)对脓毒症大鼠肺组织高迁移率族蛋白B1(HMGB1)表达的影响.方法 盲肠结扎穿孔(CLP)法制备脓毒症动物模型,150只雄性Wistar大鼠,随机分为对照组(C组)、脓毒症模型组(CLP组)和CORM-2组(n=50),分别于术后6、12、24、48、72 h处死,采用酶联免疫吸附法(ELISA)检测肺组织匀浆中HMGB1表达水平,实时荧光定量聚合酶链反应(real-time PCR)法检测肺组织匀浆中HMGB1 mRNA的表达水平;凝胶阻滞电泳分析技术(EMSA)检测肺组织STAT3

  7. Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi

    Thirugnanam, Sivasakthivel; Munirathinam, Gnanasekar; Veerapathran, Anandharaman; Dakshinamoorthy, Gajalakshmi; Reddy, Maryada V.; RAMASWAMY, KALYANASUNDARAM


    A human homologue of high mobility group box 1 (HMGB1) protein was cloned and characterized from the human filarial parasites Wuchereria bancrofti and Brugia malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed typical architectural sequence characteristics of HMGB family of proteins and consisted of only a single HMG box domain that had significant sequence similarity to the pro-inflammat...

  8. A high-mobility group box 1 that binds to DNA, enhances pro-inflammatory activity, and acts as an anti-infection molecule in black rockfish, Sebastes schlegelii.

    Xin-Peng, Zhao; Yong-Hua, Hu; Yong, Liu; Jing-Jing, Wang; Guang-Hua, Wang; Ren-Jie, Wang; Min, Zhang


    High-mobility group box (HMGB) 1 is a chromosomal protein that plays critical roles in DNA transcription, replication and repair. In addition, HMGB1 functions as a pro-inflammatory molecule in many vertebrates and invertebrates. In teleosts, very limited studies of HMGB1 have been reported. In this study, we identified a HMGB1 homologue (SsHMGB1) from black rockfish (Sebastes schlegelii) and analyzed its structure, expression and biological function. The open reading frame of SsHMGB1 is 621 bp, with a 5'-untranslated region (UTR) of 62 bp and a 3'-UTR of 645 bp. SsHMGB1 contains two typical HMG boxes and an acidic C-terminal tail. The deduced amino acid sequence of SsHMGB1 shares the highest overall identity (89.4%) with the HMGB1 of Anoplopoma fimbria. The expression of SsHMGB1 occurred in multiple tissues and was highest in the brain. Moreover, the mRNA level of SsHMGB1 in head kidney (HK) macrophages could be induced by Listonella anguillarum in a time-dependent manner. Recombinant SsHMGB1 purified from Escherichia coli (i) bound DNA fragments in a dose-dependent manner; and (ii) induced the expression of cytokines in HK macrophages, including a significant increase in TNF-α activity and enhanced mRNA level of TNF13B and IL-1 β, which are known to be involved in antibacterial defense; moreover, (iii) significantly improved the macrophage bactericidal activity together with reduced pathogen dissemination and replication of bacteria in fish kidney. These results indicated that SsHMGB1 is a novel HMGB1 that possesses apparent immunoregulatory properties and is likely to be involved in fighting bacterial infection. PMID:27492120

  9. Expression of high mobility group box 1 in the lung protection of oxygen controlled reperfusion against early ischemia-reperfusion injury with cardiopulmonary bypass in canines%氧控制性再灌注抗犬体外循环肺缺血再灌注早期损伤过程中高迁移族蛋白1的表达

    荣健; 叶升; 吴钟凯; 陈光献; 梁孟亚; 刘海; 黄伟明; 王治平


    Objective To observe the expression of high mobility group box 1 (HMGB1)in the lung protection of oxygen controlled reperfusion against ischemia-reperfusion (I/R) with cardiopulmonary bypass (CPB) in canine. Methods Fourteen healthy canines were randomly divided into two groups:control group (n=7) and test group (n=7), and received CPB. The animals in the control group received 80% FiO2 throughout the whole procedure, whereas those in the test group received 40% immediately at the declamping of aorta, and an additional 10% every 5 min later until 80% FiO2 was reached. Other procedures were the same with control group. Arterial oxygen partial pressure (PaO2) was recorded after anesthesia was completed, before and at 5, 10, 15, 20, 25 min after sternotomy, and before withdrawal of CPB. HMGB1 expression by RT-PCR and Western blot, NF-κB expression by Western blot, IL-6 and TNF-α by ELISA were analyzed just after sternotomy(T1 ), 25 min after declamping(T2) and 90 min after declamping(T3). At the same time points, malondialdehyde, myeloperoxidase activity, wet/dry mass (Mw/MD) gnd tissue pathology were analyzed. Results PaO2 was significantly lower in the test group than that in the control group at 5, 10, 15 and 20 min after aortic declamping (all P<0.05). Compared with the control group at T2 and T3, the test group was found to have lower levels in HMGB1 mRNA and protein expressions (T2:0.926 0±0.013 9 vs 1.049 6±0.030 6;T3:0.832 5±0.015 4 vs 0.989 4±0.014 4, both P<0.05; T2:0.434 5±0.074 8 vs 0.551 2±0.047 4;T3:0.449 0±0.054 1vs 0.545 5±0.040 6, both P<0.05), NF-κB protein expression in the lung tissues, IL-6 and TNF-α in serum, Mw/MD ratio, MDA level and MPO activity (all P<0.05).Pathological scores in test group at T2 and T3 were significantly lower than those in control group (T2:2.0±0.7vs 3.8 ±0.5; T3:2.6±0.6 vs 4.2 ±0.8, both P<0.05). Conclusion Oxygen controlled reperfusion possesses lung protection in early stage of I/R injury with

  10. LOV Domain-Containing F-Box Proteins:Light-Dependent Protein Degradation Modules in Arabidopsis

    Shogo Ito; Young Hun Song; Takato Imaizumi


    Plants constantly survey the surrounding environment using several sets of photoreceptors.They can sense changes in the quantity (=intensity) and quality (=wavelength) of light and use this information to adjust their physiological responses,growth,and developmental patterns.In addition to the classical photoreceptors,such as phytochromes,cryptochromes,and phototropins,ZEITLUPE (ZTL),FLAVIN-BINDING,KELCH REPEAT,F-BOX 1 (FKF1),and LOV KELCH PROTEIN 2 (LKP2) proteins have been recently identified as blue-light photoreceptors that are important for regulation of the circadian clock and photoperiodic flowering.The ZTL/FKF1/LKP2 protein family possesses a unique combination of domains:a blue-light-absorbing LOV (Light,Oxygen,or Voltage) domain along with domains involved in protein degradation.Here,we summarize recent advances in our understanding of the function of the Arabidopsis ZTL/FKF1/LKP2 proteins.We summarize the distinct photochemical properties of their LOV domains and discuss the molecular mechanisms by which the ZTL/FKF1/LKP2 proteins regulate the circadian clock and photoperiodic flowering by controlling blue-light-dependent protein degradation.

  11. Protein Foods

    ... Text Size: A A A Listen En Español Protein Foods Foods high in protein such as fish, ... the vegetarian proteins, whether they have carbohydrate. Best Protein Choices The best choices are: Plant-based proteins ...

  12. The effect and mechanism of Astragaloside IV on immune function of regulatory T cell mediated by high mobility group box 1 protein in vitro%黄芪甲苷对体外高迁移率族蛋白B1介导小鼠调节性T细胞免疫功能的影响

    黄立锋; 李金凤; 姚咏明; 张淑文; 李文雄


    Objective Based the previous studies, the present study was performed to investigate the antagonistic effects of different doses of Astragaloside IV on the immune function of Treg mediated by HMGB1 in vitro and its potential mechanism.Methods CD4+CD25-T cells isolated from the spleens of male BABL/c mice by magnetic beads were seeded on 48-well cell culture plates and were randomly divided into four groups as follows(12 holes per group). Normal control group: CD4+CD25-T cells were cultured merely. Treg group: Tregs(100μl) and CD4+CD25-T cells were co-cultured in ratio of 1:10. HMGB1+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) for 72 h and CD4+CD25-T cells were co-cultured in ratio of 1∶10. HMGB1+AST IV+Treg group: Tregs(100μl) stimulated by HMGB1(1μg/ml) and AST IV(100μg/ml)for 72 h were co-cultured with CD4+CD25-T cells in ratio of 1:10. CD4+CD25-T cells and supernatants were again collected on post-culture 72 hour. The proliferation of CD4+CD25- T cells was analyzed by MTT test, the activity of NFAT and the contents of cytokines of IL-2 released into supernatants were also determined by means of ELISA. Results When CD4+CD25-T cells were co-cultured with Tregs, the cell proliferation(0.166±0.039) and the levels of NFAT(0.156±0.035) and IL-2(2.38±0.58) in supernatant were markedly decreased as compared with those in the control group(P<0.01). However, the contrary results were found when CD4+CD25-T cells were co-cultured with Treg stimulated by HMGB1. Compared with those in the(HMGB1+Treg) group, the contrary results were showed with a dose-dependent in the(HMGB1+ASTⅣ+Treg) group.Conclusion ASTⅣcan rivalry the effects of HMGB1 on immune function of Treg in vitro, this result indicate that ASTⅣhas the therapeutic action on inflammation promoted by HMGB1.%目的:观察高迁移率族蛋白B1(HMGB1)刺激的小鼠调节性T细胞(CD4+CD25+Treg)对CD4+CD25-T细胞免疫功能的影响及黄芪甲苷(AST Ⅳ)对HMGB1介导Treg免疫功能的拮抗作用。方法采用清洁级BALB/c小鼠,活杀后分离脾脏的CD4+CD25+Treg、CD4+CD25-T细胞,将CD4+CD25-T细胞在48孔板上随机分为4组(每组12孔)培养,对照组:单纯CD4+CD25- T细胞;Treg实验组:CD25+∶CD25-按照1∶10比例加入100μl CD4+CD25+Treg与CD4+CD25-T细胞共同培养;HMGB1+Treg组:按CD25+∶CD25-比例为1∶10加入100μl经HMGB1(1μg/ml)刺激72 h的Treg与CD4+CD25-T细胞进行共培养;HMGB1+AST IV+Treg组: CD25+∶CD25-按照1∶10比例加入100μl经HMGB1(1μg/ml)、AST IV(100μg/ml)刺激72 h的CD4+CD25+Treg与CD4+CD25-T细胞共同培养。以上4组均于培养后72 h重新分离收集CD4+CD25-T细胞及其上清液,采用噻唑蓝(MTT)法检测脾脏CD4+CD25-T细胞增殖活性;ELISA法检测CD4+CD25-T细胞活化核因子(NFAT)活性、孵育上清液IL-2表达。结果将CD4+CD25+Treg加入CD4+CD25-T细胞培养后,CD4+CD25-T细胞增殖活性受到抑制(0.166±0.039),P<0.01,NFAT活性(0.156±0.035)、IL-2水平(2.38±0.58)pg/ml均较对照组下降(P<0.01)。加入经HMGB1刺激的Treg后,CD4+CD25-T细胞增殖活性受抑制程度逆转(0.477±0.097),P<0.01。与CD4+CD25+Treg组比较,HMGB1+Treg组NFAT活性(0.409±0.094)、IL-2(4.55±0.96)pg/ml均升高(P<0.01)。与HMGB1+Treg组比较,HMGB1+AST Ⅳ+Treg组CD4+CD25-T细胞增殖受抑制程度加重(0.287±0.052)、NFAT活性(0.261±0.046)、IL-2水平(2.73±0.62)pg/ml降低(P<0.01)。结论 HMGB1在体外可抑制小鼠Treg免疫功能发挥,而ASTⅣ可拮抗HMGB1对Treg免疫功能的抑制作用,表明其对HMGB1介导的促炎效应具有治疗作用。

  13. Protein-protein interactions

    Byron, Olwyn; Vestergaard, Bente


    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers. The...

  14. Synthetic high-density lipoprotein-like nanoparticles potently inhibit cell signaling and production of inflammatory mediators induced by lipopolysaccharide binding Toll-like receptor 4.

    Foit, Linda; Thaxton, C Shad


    Toll-like receptor 4 (TLR4) plays a critical role in the innate immune system. Stimulation of TLR4 occurs upon binding lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls. Due to the potency of the induced inflammatory response, there is a growing interest in agents that can most proximally modulate this LPS/TLR4 interaction to prevent downstream cell signaling events and the production of inflammatory mediators. Building on the natural ability of human high-density lipoprotein (HDL) to bind LPS, we synthesized a suite of HDL-like nanoparticles (HDL-like NP). We identified one HDL-like NP that was particularly effective at decreasing TLR4 signaling caused by addition of purified LPS or Gram-negative bacteria to model human cell lines or primary human peripheral blood cells. The HDL-like NP functioned to inhibit TLR4-dependent inflammatory response to LPS derived from multiple bacterial species. Mechanistically, data show that the NP mainly functions by scavenging and neutralizing the LPS toxin. Taken together, HDL-like NPs constitute a powerful endotoxin scavenger with the potential to significantly reduce LPS-mediated inflammation. PMID:27244690

  15. : Protein flexibility

    Bornot, Aurélie; Offmann, Bernard; De Brevern, Alexandre


    Protein structures and protein structural models are great tools to reach protein function and provide very relevant information for drug design. Nevertheless, protein structures are not rigid entities. Cutting-edge bioinformatics methods tend to take into account the flexibility of these macromolecules. We present new approaches used to define protein structure flexibility.

  16. Total protein

    The total protein test measures the total amount of two classes of proteins found in the fluid portion of your ... nutritional problems, kidney disease or liver disease . If total protein is abnormal, you will need to have more ...

  17. Interfacial Protein-Protein Associations

    Langdon, Blake B.; Kastantin, Mark; Walder, Robert; Schwartz, Daniel K.


    While traditional models of protein adsorption focus primarily on direct protein-surface interactions, recent findings suggest that protein-protein interactions may play a central role. Using high-throughput intermolecular resonance energy transfer (RET) tracking, we directly observed dynamic, protein-protein associations of bovine serum albumin on poly(ethylene glycol) modified surfaces. The associations were heterogeneous and reversible, and associating molecules resided on the surface for ...

  18. Total protein

    ... page: // Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  19. Protein Structure

    Asmus, Elaine Garbarino


    Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

  20. Tau protein

    Frederiksen, Jette Lautrup Battistini; Kristensen, Kim; Bahl, Jmc;


    Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS. Objective: To investigate the association between tau protein concentration and 14...... the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records. Results: The study shows a significantly increased...... concentration of tau protein in CSF from patients with relapsing-remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status...

  1. Protein politics

    Vijver, Marike


    This study is part of the program of the interdisciplinary research group Profetas (protein foods, environment, technology and society). Profetas consists of technological, environmental and socio-economic research projects on protein food systems which result in the development of scenarios and strategies for guiding a shift towards a more plant protein based diet. The different research projects focus on the goal of identifying viable options for a more sustainable food system. Profetas aro...

  2. Principles of protein-protein interactions.

    Jones, S; Thornton, J. M.


    This review examines protein complexes in the Brookhaven Protein Databank to gain a better understanding of the principles governing the interactions involved in protein-protein recognition. The factors that influence the formation of protein-protein complexes are explored in four different types of protein-protein complexes--homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The comparison between the complexes highlights differences tha...

  3. Protein-Protein Interaction Databases

    Szklarczyk, Damian; Jensen, Lars Juhl


    of research are explored. Here we present an overview of the most widely used protein-protein interaction databases and the methods they employ to gather, combine, and predict interactions. We also point out the trade-off between comprehensiveness and accuracy and the main pitfall scientists have to be aware...

  4. Whey Protein

    ... quality of life in people with mitochondrial diseases. Ovarian cysts (Polycystic ovarian syndrome). Early research suggests that taking ... weight, fat mass, and cholesterol in people with ovarian cysts. However, whey protein does not improve blood sugar ...

  5. Protein Crystallization

    Chernov, Alexander A.


    Nucleation, growth and perfection of protein crystals will be overviewed along with crystal mechanical properties. The knowledge is based on experiments using optical and force crystals behave similar to inorganic crystals, though with a difference in orders of magnitude in growing parameters. For example, the low incorporation rate of large biomolecules requires up to 100 times larger supersaturation to grow protein, rather than inorganic crystals. Nucleation is often poorly reproducible, partly because of turbulence accompanying the mixing of precipitant with protein solution. Light scattering reveals fluctuations of molecular cluster size, its growth, surface energies and increased clustering as protein ages. Growth most often occurs layer-by-layer resulting in faceted crystals. New molecular layer on crystal face is terminated by a step where molecular incorporation occurs. Quantitative data on the incorporation rate will be discussed. Rounded crystals with molecularly disordered interfaces will be explained. Defects in crystals compromise the x-ray diffraction resolution crucially needed to find the 3D atomic structure of biomolecules. The defects are immobile so that birth defects stay forever. All lattice defects known for inorganics are revealed in protein crystals. Contribution of molecular conformations to lattice disorder is important, but not studied. This contribution may be enhanced by stress field from other defects. Homologous impurities (e.g., dimers, acetylated molecules) are trapped more willingly by a growing crystal than foreign protein impurities. The trapped impurities induce internal stress eliminated in crystals exceeding a critical size (part of mni for ferritin, lysozyme). Lesser impurities are trapped from stagnant, as compared to the flowing, solution. Freezing may induce much more defects unless quickly amorphysizing intracrystalline water.

  6. Blockage of receptor-interacting protein 2 expression by small interfering RNA in murine macrophages


    This study aims to demonstrate that blocking the receptor-interacting protein2(Rip2)expression can decrease inflammatory cytokine production by macrophage and protect mice from endotoxin lethality.Murine Rip2 small interfering RNA(siRNA)plasmids were constructed and transfected into macrophage and Rip2 expression was detected with reverse transcription-polymerase chain reaction(RT-PCR)and western blot.Cell proliferation was assayed with MTT.TNF-α concentration was assayed with ELISA and high-mobility group box 1 protein(HMGB1)level with semi-quantitative western blot after lipopolysaccharide(LPS)stimulation.LPS challenge was given after the plasmids were injected into mice and the survival rate was calculated.Rip2 siRNA plasmid could block the mRNA and protein expression of Rip2 and promote cell proliferation.Blocking Rip2 could attenuate LPS-induced TNF-~ and HMGB1 production.The HMGB1 expression in the liver decreased to(40.21±11.03)pg/g,and serum TNF-α level decreased to(300.43±59.26)ng/L(P<0.05).The survival rate of mice from endotoxemia was also improved(P<0.05).The results demonstrate that Rip2 siRNA plasmid can block the expression of Rip2,decrease the production of TNF-α and HMGB1 and protect mice from fatal endotoxemia.

  7. Single proteins that serve linked functions in intracellular and extracellular microenvironments

    Radisky, Derek C.; Stallings-Mann, Melody; Hirai, Yohei; Bissell, Mina J.


    protein secretion (as syntaxin-2), amphoterin/high mobility group box-1 (HMGB1), which may link inflammation (as amphoterin) with regulation of gene expression (as HMGB1), and tissue transglutaminase, which affects delivery of and response to apoptotic signals by serving a related function on both sides of the plasma membrane. As it is notable that all three of these proteins have been reported to transit the plasma membrane through non-classical secretory mechanisms, we will also discuss why coordinated inside/outside functions may be found in some examples of proteins which transit the plasma membrane through non-classical mechanisms and how this relationship can be used to identify additional proteins that share these characteristics.

  8. Arabinogalactan proteins

    Knoch, Eva; Dilokpimol, Adiphol; Geshi, Naomi


    Arabinogalactan proteins (AGPs) are a highly diverse class of cell surface proteoglycans that are commonly found in most plant species. AGPs play important roles in many cellular processes during plant development, such as reproduction, cell proliferation, pattern formation and growth, and in plant...

  9. Evolution and Origin of HRS, a Protein Interacting with Merlin, the Neurofibromatosis 2 Gene Product

    Leonid V. Omelyanchuk


    Full Text Available Hepatocyte growth factor receptor tyrosine kinase substrate (HRS is an endosomal protein required for trafficking receptor tyrosine kinases from the early endosome to the lysosome. HRS interacts with Merlin, the Neurofibromatosis 2 (NF2 gene product, and this interaction may be important for Merlin’s tumor suppressor activity. Understanding the evolution, origin, and structure of HRS may provide new insight into Merlin function. We show that HRS homologs are present across a wide range of Metazoa with the yeast Vps27 protein as their most distant ancestor. The phylogenetic tree of the HRS family coincides with species evolution and divergence, suggesting a unique function for HRS. Sequence alignment shows that various protein domains of HRS, including the VHS domain, the FYVE domain, the UIM domain, and the clathrin-binding domain, are conserved from yeast to multicellular organisms. The evolutionary transition from unicellular to multicellular organisms was accompanied by the appearance of a binding site for Merlin, which emerges in the early Metazoa after its separation from flatworms. In addition to the region responsible for growth suppression, the Merlin-binding and STAM-binding domains of HRS are conserved among multicellular organisms. The residue equivalent to tyrosine-377, which is phosphorylated in the human HRS protein, is highly conserved throughout the HRS family. Three additional conserved boxes lacking assigned functions are found in the HRS proteins of Metazoa. While boxes 1 and 3 may constitute the Eps-15- and Snx1-binding sites, respectively, box 2, containing the residue equivalent to tyrosine-377, is likely to be important for HRS phosphorylation. While several functional domains are conserved throughout the HRS family, the STAM-binding, Merlin-binding, and growth suppression domains evolved in the early Metazoa around the time the Merlin protein emerged. As these domains appear during the transition to multicellularity

  10. Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

    Peng Liu; Lei Yang; Daming Shi; Xianglong Tang


    A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction net...

  11. Grafting of protein-protein binding sites


    A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of ligand protein to be grafted are identified and suitable positions in scaffold protein for grafting these key residues are sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding Ca and Cb atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position. And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein by statistical analysis of rigid binding data sets.

  12. Detecting overlapping protein complexes in protein-protein interaction networks

    Nepusz, Tamás; Yu, Haiyuan; Paccanaro, Alberto


    We introduce clustering with overlapping neighborhood expansion (ClusterONE), a method for detecting potentially overlapping protein complexes from protein-protein interaction data. ClusterONE-derived complexes for several yeast data sets showed better correspondence with reference complexes in the Munich Information Center for Protein Sequence (MIPS) catalog and complexes derived from the Saccharomyces Genome Database (SGD) than the results of seven popular methods. The results also showed a...

  13. EDITORIAL: Precision proteins Precision proteins

    Demming, Anna


    Since the birth of modern day medicine, during the times of Hippocrates in ancient Greece, the profession has developed from the rudimentary classification of disease into a rigorous science with an inspiring capability to treat and cure. Scientific methodology has distilled clinical diagnostic tools from the early arts of prognosis, which used to rely as much on revelation and prophecy, as intuition and judgement [1]. Over the past decade, research into the interactions between proteins and nanosystems has provided some ingenious and apt techniques for delving into the intricacies of anatomical systems. In vivo biosensing has emerged as a vibrant field of research, as much of medical diagnosis relies on the detection of substances or an imbalance in the chemicals in the body. The inherent properties of nanoscale structures, such as cantilevers, make them well suited to biosensing applications that demand the detection of molecules at very low concentrations. Measurable deflections in cantilevers functionalised with antibodies provide quantitative indicators of the presence of specific antigens when the two react. Such developments have roused mounting interest in the interactions of proteins with nanostructures, such as carbon nanotubes [3], which have demonstrated great potential as generic biomarkers. Plasmonic properties are also being exploited in sensing applications, such as the molecular sentinel recently devised by researchers in the US. The device uses the plasmonic properties of a silver nanoparticle linked to a Raman labelled hairpin DNA probe to signal changes in the probe geometry resulting from interactions with substances in the environment. Success stories so far include the detection of two specific genes associated with breast cancer [4]. A greater understanding of how RNA interference regulates gene expression has highlighted the potential of using this natural process as another agent for combating disease in personalized medicine. However, the

  14. Protein Crystal Based Nanomaterials

    Bell, Jeffrey A.; VanRoey, Patrick


    This is the final report on a NASA Grant. It concerns a description of work done, which includes: (1) Protein crystals cross-linked to form fibers; (2) Engineering of protein to favor crystallization; (3) Better knowledge-based potentials for protein-protein contacts; (4) Simulation of protein crystallization.

  15. Shotgun protein sequencing.

    Faulon, Jean-Loup Michel; Heffelfinger, Grant S.


    A novel experimental and computational technique based on multiple enzymatic digestion of a protein or protein mixture that reconstructs protein sequences from sequences of overlapping peptides is described in this SAND report. This approach, analogous to shotgun sequencing of DNA, is to be used to sequence alternative spliced proteins, to identify post-translational modifications, and to sequence genetically engineered proteins.

  16. Protein-protein complexation in bioluminescence

    Titushin, Maxim S.; Feng, Yingang; Lee, John; Vysotski, Eugene S.; Liu, Zhi-jie


    In this review we summarize the progress made towards understanding the role of protein-protein interactions in the function of various bioluminescence systems of marine organisms, including bacteria, jellyfish and soft corals, with particular focus on methodology used to detect and characterize these interactions. In some bioluminescence systems, protein-protein interactions involve an “accessory protein” whereby a stored substrate is efficiently delivered to the bioluminescent enzyme lucife...

  17. Protein folding, protein homeostasis, and cancer

    John H. Van Drie


    Proteins fold into their functional 3-dimensional structures from a linear amino acid sequence. In vitro this process is spontaneous; while in vivo it is orchestrated by a specialized set of proteins, called chaperones. Protein folding is an ongoing cellular process, as cellular proteins constantly undergo synthesis and degradation. Here emerging links between this process and cancer are reviewed. This perspective both yields insights into the current struggle to develop novel cancer chemotherapeutics and has implications for future chemotherapy discovery.

  18. Protein-Protein Interaction Analysis by Docking

    Stephan Ederer; Florian Fink; Wolfram Gronwald


    Based on a protein-protein docking approach we have developed a procedure to verify or falsify protein-protein interactions that were proposed by other methods such as yeast-2-hybrid assays. Our method currently utilizes intermolecular energies but can be expanded to incorporate additional terms such as amino acid based pair-potentials. We show some early results that demonstrate the general applicability of our approach.

  19. Protein-losing enteropathy

    ... this page: // Protein-losing enteropathy To use the sharing features on this page, please enable JavaScript. Protein-losing enteropathy is an abnormal loss of protein ...

  20. Protein and Heart Health

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Protein and Heart Health Updated:May 5,2015 Protein ... said. What’s the harm in getting too much protein? The main problem is that often the extra ...

  1. SPIDer: Saccharomyces protein-protein interaction database

    Li Zhenbo


    Full Text Available Abstract Background Since proteins perform their functions by interacting with one another and with other biomolecules, reconstructing a map of the protein-protein interactions of a cell, experimentally or computationally, is an important first step toward understanding cellular function and machinery of a proteome. Solely derived from the Gene Ontology (GO, we have defined an effective method of reconstructing a yeast protein interaction network by measuring relative specificity similarity (RSS between two GO terms. Description Based on the RSS method, here, we introduce a predicted Saccharomyces protein-protein interaction database called SPIDer. It houses a gold standard positive dataset (GSP with high confidence level that covered 79.2% of the high-quality interaction dataset. Our predicted protein-protein interaction network reconstructed from the GSPs consists of 92 257 interactions among 3600 proteins, and forms 23 connected components. It also provides general links to connect predicted protein-protein interactions with three other databases, DIP, BIND and MIPS. An Internet-based interface provides users with fast and convenient access to protein-protein interactions based on various search features (searching by protein information, GO term information or sequence similarity. In addition, the RSS value of two GO terms in the same ontology, and the inter-member interactions in a list of proteins of interest or in a protein complex could be retrieved. Furthermore, the database presents a user-friendly graphical interface which is created dynamically for visualizing an interaction sub-network. The database is accessible at Conclusion SPIDer is a public database server for protein-protein interactions based on the yeast genome. It provides a variety of search options and graphical visualization of an interaction network. In particular, it will be very useful for the study of inter-member interactions

  2. PIC: Protein Interactions Calculator

    Tina, KG; Bhadra, R.; Srinivasan, N.


    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bo...

  3. Drugging Membrane Protein Interactions.

    Yin, Hang; Flynn, Aaron D


    The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind cells to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally "undruggable" regions of membrane proteins, enabling modulation of protein-protein, protein-lipid, and protein-nucleic acid interactions. In this review, we survey the state of the art of high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets. PMID:26863923

  4. PREFACE: Protein protein interactions: principles and predictions

    Nussinov, Ruth; Tsai, Chung-Jung


    Proteins are the `workhorses' of the cell. Their roles span functions as diverse as being molecular machines and signalling. They carry out catalytic reactions, transport, form viral capsids, traverse membranes and form regulated channels, transmit information from DNA to RNA, making possible the synthesis of new proteins, and they are responsible for the degradation of unnecessary proteins and nucleic acids. They are the vehicles of the immune response and are responsible for viral entry into the cell. Given their importance, considerable effort has been centered on the prediction of protein function. A prime way to do this is through identification of binding partners. If the function of at least one of the components with which the protein interacts is known, that should let us assign its function(s) and the pathway(s) in which it plays a role. This holds since the vast majority of their chores in the living cell involve protein-protein interactions. Hence, through the intricate network of these interactions we can map cellular pathways, their interconnectivities and their dynamic regulation. Their identification is at the heart of functional genomics; their prediction is crucial for drug discovery. Knowledge of the pathway, its topology, length, and dynamics may provide useful information for forecasting side effects. The goal of predicting protein-protein interactions is daunting. Some associations are obligatory, others are continuously forming and dissociating. In principle, from the physical standpoint, any two proteins can interact, but under what conditions and at which strength? The principles of protein-protein interactions are general: the non-covalent interactions of two proteins are largely the outcome of the hydrophobic effect, which drives the interactions. In addition, hydrogen bonds and electrostatic interactions play important roles. Thus, many of the interactions observed in vitro are the outcome of experimental overexpression. Protein disorder

  5. Protein sequence comparison and protein evolution

    Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry


    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

  6. Prediction of Protein-Protein Interactions Using Protein Signature Profiling

    Mahmood; A.; Mahdavi; Yen-Han; Lin


    Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain inter- actions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as "interacting". In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis ele- gans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area un- der the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs in- creased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on aver- age 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.

  7. The Influence of Co-Suppressing Tomato 1-Aminocyclopropane-1-Carboxylic Acid Oxidase Ⅰ on the Expression of Fruit Ripening-Related and Pathogenesis-Related Protein Genes

    HU Zong-li; CHEN Xu-qing; CHEN Guo-ping; L(U) Li-juan; Grierson Donald


    The purpose of this study is to explore the influence of co-suppressing tomato ACC oxidase I on the expression of fruit ripening-related and pathogenesis-related protein genes, and on the biosynthesis of endogenous ethylene and storage ability of fruits. Specific fragments of several fruit ripening-related and pathogenesis-related protein genes from tomato (Lycopersicon esculentum) were cloned, such as the 1-aminocyclopropane-1-carboxylic acid oxidase 1 gene (LeACO1), 1-aminocyclopropane-1-carboxylic acid oxidase 3 gene (LeAC03), EIN3-binding F-box 1 gene (LeEBF1), pathogenesisrelated protein 1 gene (LePR1), pathogenesis-related protein 5 gene (LePR5), and pathogenesis-related protein osmotin precursor gene (LeNP24) by PCR or RT-PCR. Then these specific DNA fragments were used as probes to hybridize with the total RNAs extracted from the wild type tomato Ailsa Craig (AC++) and the LeACO1 co-suppression tomatoes (V1187 and T4B), respectively. At the same time, ethylene production measurement and storage experiment of tomato fruits were carried out. The hybridization results indicated that the expression of fruit ripening-related genes such as LeACO3 and LeEBF1, and pathogenesis-related protein genes such as LePR1, LePR5, and LeNP24, were reduced sharply, and the ethylene production in the fruits, wounded leaves decreased and the storage time of ripening fruits was prolonged, when the expression of LeACO1 gene in the transgenic tomato was suppressed. In the co-suppression tomatoes, the expression of fruit ripening-related and pathogenesis-related protein genes were restrained at different degrees, the biosynthesis of endogenous ethylene decreased and the storage ability of tomato fruits increased.

  8. Urine Protein and Urine Protein to Creatinine Ratio

    ... limited. Home Visit Global Sites Search Help? Urine Protein and Urine Protein to Creatinine Ratio Share this page: Was this page helpful? Also known as: 24-Hour Urine Protein; Urine Total Protein; Urine Protein to Creatinine Ratio; ...

  9. Protein- protein interaction detection system using fluorescent protein microdomains

    Waldo, Geoffrey S.; Cabantous, Stephanie


    The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

  10. IGSF9 Family Proteins

    Hansen, Maria; Walmod, Peter Schledermann


    The Drosophila protein Turtle and the vertebrate proteins immunoglobulin superfamily (IgSF), member 9 (IGSF9/Dasm1) and IGSF9B are members of an evolutionarily ancient protein family. A bioinformatics analysis of the protein family revealed that invertebrates contain only a single IGSF9 family gene......, whereas vertebrates contain two to four genes. In cnidarians, the gene appears to encode a secreted protein, but transmembrane isoforms of the protein have also evolved, and in many species, alternative splicing facilitates the expression of both transmembrane and secreted isoforms. In most species, the...... longest isoforms of the proteins have the same general organization as the neural cell adhesion molecule family of cell adhesion molecule proteins, and like this family of proteins, IGSF9 family members are expressed in the nervous system. A review of the literature revealed that Drosophila Turtle...

  11. Surface Mediated Protein Disaggregation

    Radhakrishna, Mithun; Kumar, Sanat K.


    Preventing protein aggregation is of both biological and industrial importance. Biologically these aggregates are known to cause amyloid type diseases like Alzheimer's and Parkinson's disease. Protein aggregation leads to reduced activity of the enzymes in industrial applications. Inter-protein interactions between the hydrophobic residues of the protein are known to be the major driving force for protein aggregation. In the current paper we show how surface chemistry and curvature can be tuned to mitigate these inter-protein interactions. Our results calculated in the framework of the Hydrophobic-Polar (HP) lattice model show that, inter-protein interactions can be drastically reduced by increasing the surface hydrophobicity to a critical value corresponding to the adsorption transition of the protein. At this value of surface hydrophobicity, proteins lose inter-protein contacts to gain surface contacts and thus the surface helps in reducing the inter-protein interactions. Further, we show that the adsorption of the proteins inside hydrophobic pores of optimal sizes are most efficient both in reducing inter-protein contacts and simultaneously retaining most of the native-contacts due to strong protein-surface interactions coupled with stabilization due to the confinement. Department of Energy (Grant No DE-FG02-11ER46811).

  12. Discover protein sequence signatures from protein-protein interaction data

    Haasl Ryan J


    Full Text Available Abstract Background The development of high-throughput technologies such as yeast two-hybrid systems and mass spectrometry technologies has made it possible to generate large protein-protein interaction (PPI datasets. Mining these datasets for underlying biological knowledge has, however, remained a challenge. Results A total of 3108 sequence signatures were found, each of which was shared by a set of guest proteins interacting with one of 944 host proteins in Saccharomyces cerevisiae genome. Approximately 94% of these sequence signatures matched entries in InterPro member databases. We identified 84 distinct sequence signatures from the remaining 172 unknown signatures. The signature sharing information was then applied in predicting sub-cellular localization of yeast proteins and the novel signatures were used in identifying possible interacting sites. Conclusion We reported a method of PPI data mining that facilitated the discovery of novel sequence signatures using a large PPI dataset from S. cerevisiae genome as input. The fact that 94% of discovered signatures were known validated the ability of the approach to identify large numbers of signatures from PPI data. The significance of these discovered signatures was demonstrated by their application in predicting sub-cellular localizations and identifying potential interaction binding sites of yeast proteins.

  13. Polymer Directed Protein Assemblies

    Patrick van Rijn


    Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

  14. Protein Dynamics in an RNA Binding Protein

    Hall, Kathleen


    Using ^15N NMR relaxation measurements, analyzed with the Lipari-Szabo formalism, we have found that the human U1A RNA binding protein has ps-ns motions in those loops that make contact with RNA. Specific mutations can alter the extent and pattern of motions, and those proteins inevitably lose RNA binding affinity. Proteins with enhanced mobility of loops and termini presumably lose affinity due to increased conformational sampling by those parts of the protein that interact directly with RNA. There is an entropic penalty associated with locking down those elements upon RNA binding, in addition to a loss of binding efficiency caused by the increased number of conformations adopted by the protein. However, in addition to local conformational heterogeneity, analysis of molecular dynamics trajectories by Reorientational Eigenmode Dynamics reveals that loops of the wild type protein undergo correlated motions that link distal sites across the binding surface. Mutations that disrupt correlated motions result in weaker RNA binding, implying that there is a network of interactions across the surface of the protein. (KBH was a Postdoctoral Fellow with Al Redfield from 1985-1990). This work was supported by the NIH (to KBH) and NSF (SAS).

  15. Anisotropic Contributions to Protein-Protein Interactions.

    Quang, Leigh J; Sandler, Stanley I; Lenhoff, Abraham M


    The anisotropy of shape and functionality of proteins complicates the prediction of protein-protein interactions. We examine the distribution of electrostatic and nonelectrostatic contributions to these interactions for two globular proteins, lysozyme and chymosin B, which differ in molecular weight by about a factor of 2. The interaction trends for these proteins are computed in terms of contributions to the osmotic second virial coefficient that are evaluated using atomistic models of the proteins. Our emphasis is on identifying the orientational configurations that contribute most strongly to the overall interactions due to high-complementarity interactions, and on calculating the effect of ionic strength on such interactions. The results emphasize the quantitative importance of several features of protein interactions, notably that despite differences in their frequency of occurrence, configurations differing appreciably in interaction energy can contribute meaningfully to overall interactions. However, relatively small effects due to charge anisotropy or specific hydration can affect the overall interaction significantly only if they contribute to strongly attractive configurations. The results emphasize the necessity of accounting for detailed anisotropy to capture actual experimental trends, and the sensitivity of even very detailed atomistic models to subtle solution contributions. PMID:26580057

  16. Protein Data Bank (PDB)

    U.S. Department of Health & Human Services — The Protein Data Bank (PDB) archive is the single worldwide repository of information about the 3D structures of large biological molecules, including proteins and...

  17. [Protein-losing enteropathy].

    Amiot, A


    Protein-losing enteropathy is a rare syndrome of gastrointestinal protein loss. The primary causes can be classified into lymphatic leakage due to increased interstitial pressure and increased leakage of protein-rich fluids due to erosive or non-erosive gastrointestinal disorders. The diagnosis of protein-losing enteropathy should be considered in patients with chronic diarrhea and peripheral oedema. The diagnosis of protein-losing enteropathy is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Most protein-losing enteropathy cases are the result of either lymphatic obstruction or a variety of gastrointestinal disorders and cardiac diseases, while primary intestinal lymphangiectasia (Waldmann's disease) is less common. Treatment of protein-losing enteropathy targets the underlying disease but also includes dietary modification, such as high-protein and low-fat diet along with medium-chain triglyceride supplementation. PMID:25618488

  18. Protein (Cyanobacteria): 360792 [

    Full Text Available YP_007146453.1 1117:17211 1161:2741 1162:3098 56106:1490 142864:1490 56107:1490 putative stress ... protein (general stress ... protein 26) Cylindrospermum stagnale PCC 7417 MTTS ...

  19. Hydrodynamic effects in proteins

    Szymczak, Piotr; Cieplak, Marek


    Experimental and numerical results pertaining to flow-induced effects in proteins are reviewed. Special emphasis is placed on shear-induced unfolding and on the role of solvent mediated hydrodynamic interactions in the conformational transitions in proteins.

  20. Hydrodynamic effects in proteins

    Szymczak, Piotr [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw, Hoza 69, 00-681 Warsaw (Poland); Cieplak, Marek, E-mail: [Institute of Physics, Polish Academy of Sciences, Aleja Lotnikow 32/46, 02-668 Warsaw (Poland)


    Experimental and numerical results pertaining to flow-induced effects in proteins are reviewed. Special emphasis is placed on shear-induced unfolding and on the role of solvent mediated hydrodynamic interactions in the conformational transitions in proteins. (topical review)

  1. Protein electrophoresis - serum

    ... this page: // Protein electrophoresis - serum To use the sharing features on ... JavaScript. This lab test measures the types of protein in the fluid (serum) part of a blood ...

  2. Protein: CAD [Trypanosomes Database

    Full Text Available CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotaseCAD trifunct ... ional protein carbamoylphosphate synthetase 2/aspartate transcarb ... amylase/dihydroorotasemultifunctional protein ... CAD H.sapiens 47458828 18105007 790 P27708 CAD_(ge ...

  3. Learning about Proteins

    ... need from peanuts alone, but if you have peanut butter on whole-grain bread, you're set. Likewise, ... protein in a day: 2 tablespoons (15 milliliters) peanut butter (7 grams protein) 1 cup (240 milliliters) low- ...

  4. Electrophoretic Separation of Proteins

    Chakavarti, Bulbul; Chakavarti, Deb


    Electrophoresis is used to separate complex mixtures of proteins (e.g., from cells, subcellular fractions, column fractions, or immunoprecipitates), to investigate subunit compositions, and to verify homogeneity of protein samples. It can also serve to purify proteins for use in further applications. In polyacrylamide gel electrophoresis, proteins migrate in response to an electrical field through pores in a polyacrylamide gel matrix; pore size decreases with increasing acrylamide concentrati...

  5. Simulations of protein folding

    We have developed a simple, phenomenological, Monte-Carlo code that predicts the three-dimensional structure of globular proteins from the DNA sequences that define them. We have applied this code to two small proteins, the villin headpiece (1VII) and colel rop (1ROP). Our code folds both proteins to within 5 A rms of their native structures

  6. Destabilized bioluminescent proteins

    Allen, Michael S.; Rakesh, Gupta; Gary, Sayler S.


    Purified nucleic acids, vectors and cells containing a gene cassette encoding at least one modified bioluminescent protein, wherein the modification includes the addition of a peptide sequence. The duration of bioluminescence emitted by the modified bioluminescent protein is shorter than the duration of bioluminescence emitted by an unmodified form of the bioluminescent protein.

  7. Protein domain prediction

    Ingolfsson, Helgi; Yona, Golan


    Domains are considered to be the building blocks of protein structures. A protein can contain a single domain or multiple domains, each one typically associated with a specific function. The combination of domains determines the function of the protein, its subcellular localization and the interacti

  8. CSF total protein

    CSF total protein is a test to determine the amount of protein in your spinal fluid, also called cerebrospinal fluid (CSF). ... The normal protein range varies from lab to lab, but is typically about 15 to 60 mg/dL. Note: mg/dL = ...

  9. Modeling Protein Domain Function

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth


    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  10. Protein - Which is Best?

    Hoffman, Jay R; Falvo, Michael J


    Protein intake that exceeds the recommended daily allowance is widely accepted for both endurance and power athletes. However, considering the variety of proteins that are available much less is known concerning the benefits of consuming one protein versus another. The purpose of this paper is to identify and analyze key factors in order to make responsible recommendations to both the general and athletic populations. Evaluation of a protein is fundamental in determining its appropriateness in the human diet. Proteins that are of inferior content and digestibility are important to recognize and restrict or limit in the diet. Similarly, such knowledge will provide an ability to identify proteins that provide the greatest benefit and should be consumed. The various techniques utilized to rate protein will be discussed. Traditionally, sources of dietary protein are seen as either being of animal or vegetable origin. Animal sources provide a complete source of protein (i.e. containing all essential amino acids), whereas vegetable sources generally lack one or more of the essential amino acids. Animal sources of dietary protein, despite providing a complete protein and numerous vitamins and minerals, have some health professionals concerned about the amount of saturated fat common in these foods compared to vegetable sources. The advent of processing techniques has shifted some of this attention and ignited the sports supplement marketplace with derivative products such as whey, casein and soy. Individually, these products vary in quality and applicability to certain populations. The benefits that these particular proteins possess are discussed. In addition, the impact that elevated protein consumption has on health and safety issues (i.e. bone health, renal function) are also reviewed. Key PointsHigher protein needs are seen in athletic populations.Animal proteins is an important source of protein, however potential health concerns do exist from a diet of protein

  11. Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

    Jong-Sup Bae


    Full Text Available High mobility group box 1 (HMGB1 is involved in thepathogenesis of vascular diseases. Unlike activated protein C(APC, the activation of PAR-1 by thrombin is known to elicitproinflammatory responses. To determine whether the occupancyof EPCR by the Gla-domain of APC is responsible for thePAR-1-dependent antiinflammatory activity of the protease, wepretreated HUVECs with the PC zymogen and then activatedPAR-1 with thrombin. It was found that thrombin downregulatesthe HMGB1-mediated induction of both TNF-α andIL-6 and inhibits the activation of both p38 MAPK and NF-κB inHUVECs pretreated with PC. Furthermore, thrombin inhibitedHMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion moleculesin HUVECs if EPCR was occupied. Collectively, theseresults suggest the concept that thrombin can initiate proinflammatoryresponses in vascular endothelial cells through theactivation of PAR-1 may not hold true for normal vesselsexpressing EPCR under in vivo conditions. [BMB Reports 2013;46(11: 544-549

  12. Highly thermostable fluorescent proteins

    Bradbury, Andrew M.; Waldo, Geoffrey S.; Kiss, Csaba


    Thermostable fluorescent proteins (TSFPs), methods for generating these and other stability-enhanced proteins, polynucleotides encoding such proteins, and assays and method for using the TSFPs and TSFP-encoding nucleic acid molecules are provided. The TSFPs of the invention show extremely enhanced levels of stability and thermotolerance. In one case, for example, a TSFP of the invention is so stable it can be heated to C. for short periods of time without denaturing, and retains 85% of its fluorescence when heated to C. for several minutes. The invention also provides a method for generating stability-enhanced variants of a protein, including but not limited to fluorescent proteins.

  13. Protein hydration and dynamics

    Inelastic neutron scattering can measure the protein thermal fluctuations under the physiological aqueous environment, especially it is powerful to observe the low-energy protein dynamics in THz region, which are revealed theoretically to be coupled with solvations. Neutron enables the selective observation of protein and hydration water by deuteration. The complementary analysis with molecular dynamics simulation is also effective for the study of protein hydration. Some examples of the application toward the understanding of molecular basis of protein functions will be introduced. (author)

  14. Protein crystallization with paper

    Matsuoka, Miki; Kakinouchi, Keisuke; Adachi, Hiroaki; Maruyama, Mihoko; Sugiyama, Shigeru; Sano, Satoshi; Yoshikawa, Hiroshi Y.; Takahashi, Yoshinori; Yoshimura, Masashi; Matsumura, Hiroyoshi; Murakami, Satoshi; Inoue, Tsuyoshi; Mori, Yusuke; Takano, Kazufumi


    We developed a new protein crystallization method that incorporates paper. A small piece of paper, such as facial tissue or KimWipes, was added to a drop of protein solution in the traditional sitting drop vapor diffusion technique, and protein crystals grew by incorporating paper. By this method, we achieved the growth of protein crystals with reducing osmotic shock. Because the technique is very simple and the materials are easy to obtain, this method will come into wide use for protein crystallization. In the future, it could be applied to nanoliter-scale crystallization screening on a paper sheet such as in inkjet printing.

  15. Protein and vegetarian diets.

    Marsh, Kate A; Munn, Elizabeth A; Baines, Surinder K


    A vegetarian diet can easily meet human dietary protein requirements as long as energy needs are met and a variety of foods are eaten. Vegetarians should obtain protein from a variety of plant sources, including legumes, soy products, grains, nuts and seeds. Eggs and dairy products also provide protein for those following a lacto-ovo-vegetarian diet. There is no need to consciously combine different plant proteins at each meal as long as a variety of foods are eaten from day to day, because the human body maintains a pool of amino acids which can be used to complement dietary protein. The consumption of plant proteins rather than animal proteins by vegetarians may contribute to their reduced risk of chronic diseases such as diabetes and heart disease. PMID:25369930

  16. Protein kinesis: The dynamics of protein trafficking and stability



    The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

  17. Protein Electrophoresis/Immunofixation Electrophoresis

    ... be limited. Home Visit Global Sites Search Help? Protein Electrophoresis Immunofixation Electrophoresis Share this page: Was this page helpful? Also known as: Serum Protein Electrophoresis; Protein ELP; SPE; SPEP; Urine Protein Electrophoresis; ...

  18. Protein: FEB6 [TP Atlas

    Full Text Available FEB6 Photoresponse regulatory proteins HD1 SE1 Zinc finger protein HD1 Protein CONSTANS-like, Pr ... otein HEADING DATE 1, Protein PHOTOPERIOD SENSITIVITY ... 1 39947 Oryza sativa subsp. japonica 4340746 Q9FDX ...

  19. Identifying novel protein phenotype annotations by hybridizing protein-protein interactions and protein sequence similarities.

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong


    Studies of protein phenotypes represent a central challenge of modern genetics in the post-genome era because effective and accurate investigation of protein phenotypes is one of the most critical procedures to identify functional biological processes in microscale, which involves the analysis of multifactorial traits and has greatly contributed to the development of modern biology in the post genome era. Therefore, we have developed a novel computational method that identifies novel proteins associated with certain phenotypes in yeast based on the protein-protein interaction network. Unlike some existing network-based computational methods that identify the phenotype of a query protein based on its direct neighbors in the local network, the proposed method identifies novel candidate proteins for a certain phenotype by considering all annotated proteins with this phenotype on the global network using a shortest path (SP) algorithm. The identified proteins are further filtered using both a permutation test and their interactions and sequence similarities to annotated proteins. We compared our method with another widely used method called random walk with restart (RWR). The biological functions of proteins for each phenotype identified by our SP method and the RWR method were analyzed and compared. The results confirmed a large proportion of our novel protein phenotype annotation, and the RWR method showed a higher false positive rate than the SP method. Our method is equally effective for the prediction of proteins involving in all the eleven clustered yeast phenotypes with a quite low false positive rate. Considering the universality and generalizability of our supporting materials and computing strategies, our method can further be applied to study other organisms and the new functions we predicted can provide pertinent instructions for the further experimental verifications. PMID:26728152

  20. Sensitizing properties of proteins

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott;


    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding the...... relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... scientists from academia, government, and industry participated in the symposium. Experts provided overviews on known mechanisms by which proteins in food may cause sensitization, discussed experimental models to predict protein sensitizing potential, and explored whether such experimental techniques may be...

  1. NMR of unfolded proteins

    Amarnath Chtterjee; Ashutosh Kumar; Jeetender Chugh; Sudha Srivastava; Neel S Bhavesh; Ramakrishna V Hosur


    In the post-genomic era, as more and more genome sequences are becoming known and hectic efforts are underway to decode the information content in them, it is becoming increasingly evident that flexibility in proteins plays a crucial role in many of the biological functions. Many proteins have intrinsic disorder either wholly or in specific regions. It appears that this disorder may be important for regulatory functions of the proteins, on the one hand, and may help in directing the folding process to reach the compact native state, on the other. Nuclear magnetic resonance (NMR) has over the last two decades emerged as the sole, most powerful technique to help characterize these disordered protein systems. In this review, we first discuss the significance of disorder in proteins and then describe the recent developments in NMR methods for their characterization. A brief description of the results obtained on several disordered proteins is presented at the end.

  2. Computational Protein Design

    Johansson, Kristoffer Enøe

    to a central method that enables new developments. For example, novel enzymes with functions not found in natural proteins have been de novo designed to give enough activity for experimental optimization. This thesis presents the current state-of-the-art within computational design methods together......Proteins are the major functional group of molecules in biology. The impact of protein science on medicine and chemical productions is rapidly increasing. However, the greatest potential remains to be realized. The fi eld of protein design has advanced computational modeling from a tool of support...... with a novel method based on probability theory. With the aim of assembling a complete pipeline for protein design, this work touches upon several aspects of protein design. The presented work is the computational half of a design project where the other half is dedicated to the experimental part of...

  3. Protein Models Comparator

    Widera, Paweł


    The process of comparison of computer generated protein structural models is an important element of protein structure prediction. It has many uses including model quality evaluation, selection of the final models from a large set of candidates or optimisation of parameters of energy functions used in template free modelling and refinement. Although many protein comparison methods are available online on numerous web servers, their ability to handle a large scale model comparison is often very limited. Most of the servers offer only a single pairwise structural comparison, and they usually do not provide a model-specific comparison with a fixed alignment between the models. To bridge the gap between the protein and model structure comparison we have developed the Protein Models Comparator (pm-cmp). To be able to deliver the scalability on demand and handle large comparison experiments the pm-cmp was implemented "in the cloud". Protein Models Comparator is a scalable web application for a fast distributed comp...

  4. Protein oxidation and peroxidation.

    Davies, Michael J


    Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals and chain reactions with alcohols and carbonyls as major products; the latter are commonly used markers of protein damage. Direct oxidation of cysteine (and less commonly) methionine residues is a major reaction; this is typically faster than with H2O2, and results in altered protein activity and function. Unlike H2O2, which is rapidly removed by protective enzymes, protein peroxides are only slowly removed, and catabolism is a major fate. Although turnover of modified proteins by proteasomal and lysosomal enzymes, and other proteases (e.g. mitochondrial Lon), can be efficient, protein hydroperoxides inhibit these pathways and this may contribute to the accumulation of modified proteins in cells. Available evidence supports an association between protein oxidation and multiple human pathologies, but whether this link is causal remains to be established. PMID:27026395

  5. Proteins at interfaces

    Evers, Florian


    Protein adsorption is a fundamental and ubiquitous phenomenon, which has severe implications in the fields of biomaterials as well as bio- and nanotechnology, e.g., in drug delivery, biofouling, the biocompatibility of implants, food chemistry, and biosensors. Therefore, the mechanisms of protein adsorption and controlling the interfacial affinity of proteins have become intriguing and interdisciplinary research topics. In this work, X-ray and neutron reflectometry are the main...

  6. Protein-surfactant interactions

    Valstar, Ank


    Protein-surfactant interactions in aqueous media have been investigated. The globular proteins lysozyme and bovine serum albumin (BSA) served as model proteins. Several ionic and non-ionic surfactants were used. Fluorescence probe measurements showed that at low sodium dodecyl sulfate (SDS) concentration (< 0.1 M) one micelle-like SDS cluster is bound to lysozyme. From dynamic light scattering (DLS) results it was observed that lysozyme in the complex does not correspond to the fully unfol...

  7. Pressure cryocooling protein crystals

    Kim, Chae Un; Gruner, Sol M.


    Preparation of cryocooled protein crystal is provided by use of helium pressurizing and cryocooling to obtain cryocooled protein crystal allowing collection of high resolution data and by heavier noble gas (krypton or xenon) binding followed by helium pressurizing and cryocooling to obtain cryocooled protein crystal for collection of high resolution data and SAD phasing simultaneously. The helium pressurizing is carried out on crystal coated to prevent dehydration or on crystal grown in aqueous solution in a capillary.

  8. Biofilm Matrix Proteins

    Fong, Jiunn N. C.; Yildiz, Fitnat H.


    Proteinaceous components of the biofilm matrix include secreted extracellular proteins, cell surface adhesins and protein subunits of cell appendages such as flagella and pili. Biofilm matrix proteins play diverse roles in biofilm formation and dissolution. They are involved in attaching cells to surfaces, stabilizing the biofilm matrix via interactions with exopolysaccharide and nucleic acid components, developing three-dimensional biofilm architectures, and dissolving biofilm matrix via enz...

  9. Ribosome-inactivating proteins

    Walsh, Matthew J; Dodd, Jennifer E; Hautbergue, Guillaume M.


    Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the eukaryotic 60S ribosomal subunit. In this review, we compare archetypal RIP family members with oth...

  10. Trisulfides in Proteins

    Nielsen, Rasmus W.; Tachibana, Christine; Hansen, Niels Erik;


    post-translational modification, and the number of proteins in which a trisulfide has been unambiguously identified is small. Nevertheless, we believe that its prevalence may be underestimated, particularly with the increasing evidence for significant pools of sulfides in living tissues and their...... possible roles in cellular metabolism. This review focuses on examples of proteins that are known to contain a trisulfide bridge, and gives an overview of the chemistry of trisulfide formation, and the methods by which it is detected in proteins....

  11. Staining Proteins in Gels

    Gallagher, Sean; Chakavarti, Deb


    Following separation by electrophoretic methods, proteins in a gel can be detected by several staining methods. This unit describes protocols for detecting proteins by four popular methods. Coomassie blue staining is an easy and rapid method. Silver staining, while more time consuming, is considerably more sensitive and can thus be used to detect smaller amounts of protein. Fluorescent staining is a popular alternative to traditional staining procedures, mainly because it is more sensitive th...

  12. Acanthamoeba castellanii STAT protein.

    Kicinska, Anna; Leluk, Jacek; Jarmuszkiewicz, Wieslawa


    STAT (signal transducers and activators of transcription) proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil), a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds) or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups. PMID:25338074

  13. Acanthamoeba castellanii STAT protein.

    Anna Kicinska

    Full Text Available STAT (signal transducers and activators of transcription proteins are one of the important mediators of phosphotyrosine-regulated signaling in metazoan cells. We described the presence of STAT protein in a unicellular, free-living amoebae with a simple life cycle, Acanthamoeba castellanii. A. castellanii is the only, studied to date, Amoebozoan that does not belong to Mycetozoa but possesses STATs. A sequence of the A. castellanii STAT protein includes domains similar to those of the Dictyostelium STAT proteins: a coiled coil (characteristic for Dictyostelium STAT coiled coil, a STAT DNA-binding domain and a Src-homology domain. The search for protein sequences homologous to A. castellanii STAT revealed 17 additional sequences from lower eukaryotes. Interestingly, all of these sequences come from Amoebozoa organisms that belong to either Mycetozoa (slime molds or Centramoebida. We showed that there are four separated clades within the slime mold STAT proteins. The A. castellanii STAT protein branches next to a group of STATc proteins from Mycetozoa. We also demonstrate that Amoebozoa form a distinct monophyletic lineage within the STAT protein world that is well separated from the other groups.

  14. Consensus protein design

    Porebski, Benjamin T.; Buckle, Ashley M.


    A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID:27274091

  15. Engineering therapeutic protein disaggregases

    Shorter, James


    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  16. Simulations of Protein Folding

    Cahill, M; Cahill, K E; Cahill, Michael; Fleharty, Mark; Cahill, Kevin


    We have developed a simple, phenomenological, Monte-Carlo code that predicts the three-dimensional structure of globular proteins from the DNA sequences that define them. We have applied this code to two small proteins, the villin headpiece (1VII) and cole1 rop (1ROP). Our code folded the 36-residue villin headpiece to a mean rms distance of less than 5 A from its native structure as revealed by NMR; it folded a 56-residue fragment of the protein cole1 rop to within 11 A of its native structure. The denatured starting configurations of these two proteins were, respectively, 29 A and 55 A distant from their native structures.

  17. Ultrafiltration of pegylated proteins

    Molek, Jessica R.

    There is considerable clinical interest in the use of "second-generation" therapeutics produced by conjugation of a native protein with various polymers including polyethylene glycol (PEG). PEG--protein conjugates, so-called PEGylated proteins, can exhibit enhanced stability, half-life, and bioavailability. One of the challenges in the commercial production of PEGylated proteins is the purification required to remove unreacted polymer, native protein, and in many cases PEGylated proteins with nonoptimal degrees of conjugation. The overall objective of this thesis was to examine the use of ultrafiltration for the purification of PEGylated proteins. This included: (1) analysis of size-based separation of PEGylated proteins using conventional ultrafiltration membranes, (2) use of electrically-charged membranes to exploit differences in electrostatic interactions, and (3) examination of the effects of PEGylation on protein fouling. The experimental results were analyzed using appropriate theoretical models, with the underlying physical properties of the PEGylated proteins evaluated using size exclusion chromatography, capillary electrophoresis, dynamic light scattering, and reverse phase chromatography. PEGylated proteins were produced by covalent attachment of activated PEG to a protein via primary amines on the lysine residues. A simple model was developed for the reaction kinetics, which was used to explore the effect of reaction conditions and mode of operation on the distribution of PEGylated products. The effective size of the PEGylated proteins was evaluated using size exclusion chromatography, with appropriate correlations developed for the size in terms of the molecular weight of the native protein and attached PEG. The electrophoretic mobility of the PEGylated proteins were evaluated by capillary electrophoresis with the data in good agreement with a simple model accounting for the increase in protein size and the reduction in the number of protonated amine

  18. How Many Protein-Protein Interactions Types Exist in Nature?

    Garma, Leonardo; Mukherjee, Srayanta; Mitra, Pralay; Zhang, Yang


    Protein quaternary structure universe” refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the pro...

  19. How Many Protein-Protein Interactions Types Exist in Nature?

    Leonardo Garma; Srayanta Mukherjee; Pralay Mitra; Yang Zhang


    "Protein quaternary structure universe" refers to the ensemble of all protein-protein complexes across all organisms in nature. The number of quaternary folds thus corresponds to the number of ways proteins physically interact with other proteins. This study focuses on answering two basic questions: Whether the number of protein-protein interactions is limited and, if yes, how many different quaternary folds exist in nature. By all-to-all sequence and structure comparisons, we grouped the pro...

  20. High Mobility Group Box-1 Promotes Inflammation-Induced Lymphangiogenesis via Toll-Like Receptor 4-Dependent Signalling Pathway

    Zhao, Miying; Fan, Yiming; Li, Xiaorong


    Lymphangiogenesis in inflammation has received considerable attention in recent years. Administration of modulating lymphangiogenesis provides more possibilities of treating inflammation-associated diseases. However, the main mediators and factors governing inflammation-induced lymphangiogenesis (ILA) are yet to be defined. Here, we explored the role of HMGB1-TLR4 signalling pathway in modulating inflammation-induced lymphangiogenesis and its underlying mechanisms using an ILA mouse model and 2 cell lines. Our results show that HMGB1 promoted VEGF-C-induced HDLECs proliferation in a dose-dependent manner and TLR4 mediates HMGB1-induced LECs proliferation and tube formation in vitro. And in vivo, rHMGB1 treatment significantly promoted ILA, and the promoting effects was inhibited notably when HMGB1-TLR4 was blocked. HMGB1-associated ILA is primarily dependent on TLR4 but not on TLR2. In mechanisms, the recruitment and activation of CD11b+ cells are important cellular mechanisms in HMGB1-TLR4 associated ILA, and multiple key pro-lymphangiogenesis molecules mediates HMGB1-TLR4 associated ILA, including VEGF-C/VEGFR3, inflammatory factors IL-1β and TNF-α, MMP-2 and MMP-9 and NF-κB p65. In conclusion, HMGB1-associated ILA is primarily dependent on TLR4, and CD11b+ cells and multiple molecular mechanisms mediate HMGB1-TLR4 associated ILA. Furthermore, the ILA can be effectively modulated by HMGB1-TLR4 signalling. Consequently, administration of modulating ILA through HMGB1-TLR4 pathway may provide us more possibilities of treating inflammation and lymphangiogenesis associated diseases. PMID:27100831

  1. Protein (Cyanobacteria): 286011 [

    Full Text Available YP_007057271.1 1117:4890 1161:684 1185:224 373984:129 373994:129 histidine kinase,PAS ... domain-con ... taining protein,PAS ... domain-containing protein,histidine kinase,GAF dom ...

  2. Protein (Viridiplantae): 357488463 [

    Full Text Available XP_003614519.1 33090:2423 35493:1202 131221:1202 3193:1202 58023:2056 78536:1595 58024:1595 3398 ... 938 3814:1938 163742:3028 3877:3028 3880:3028 Cyst nematode ... resistance protein-like protein Medicago truncatul ...

  3. Poxviral Ankyrin Proteins

    Michael H. Herbert


    Full Text Available Multiple repeats of the ankyrin motif (ANK are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.

  4. Protein (Viridiplantae): 186478918 [

    Full Text Available NP_001117362.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  5. Protein (Viridiplantae): 145336153 [

    Full Text Available NP_174031.2 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 71 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  6. Protein (Viridiplantae): 186478920 [

    Full Text Available NP_001117363.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  7. Protein (Viridiplantae): 18396209 [

    Full Text Available NP_564271.1 33090:264 35493:490 131221:490 3193:490 58023:763 78536:5554 58024:5554 3398:5554 71 ... 88 3699:588 3700:588 980083:588 3701:588 3702:2514 StaR -like protein domain-containing protein Arabidopsis ...

  8. Proteins in biomass streams

    Mulder, W.J.


    The focus of this study is to give an overview of traditional and new biomasses and biomass streams that contain proteins. When information was available, the differences in molecular structure and physical and chemical properties for the different proteins is given. For optimal biomass use, isolati

  9. Protein (Cyanobacteria): 187726 [

    Full Text Available ZP_00515693.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MHKIPVT ...

  10. Protein (Cyanobacteria): 187721 [

    Full Text Available ZP_00515086.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MSGINQQ ...

  11. Protein (Cyanobacteria): 187724 [

    Full Text Available ZP_00514782.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MQIVDKK ...

  12. Protein (Cyanobacteria): 187722 [

    Full Text Available ZP_00515750.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MTPLNFN ...

  13. Protein (Cyanobacteria): 187723 [

    Full Text Available ZP_00515087.1 1117:3739 1118:294 263510:556 263511:556 165597:1102 Cobalamin synthesis ... protein/P ... 47K:Cobalamin synthesis ... protein/P47K Crocosphaera watsonii WH 8501 MTRLDFN ...

  14. Protein (Viridiplantae): 15240110 [

    Full Text Available NP_201488.1 33090:325 35493:1944 131221:1944 3193:1944 58023:3713 78536:2650 58024:2650 3398:265 ... :1852 LOB domain-containing protein 36 (ASYMMETRIC LEAVES ... 2-like protein 1) Arabidopsis thaliana MASSSSPCAAC ...

  15. Protein (Viridiplantae): 357505877 [

    Full Text Available XP_003623227.1 33090:2309 35493:2314 131221:2314 3193:2314 58023:1780 78536:1486 58024:1486 3398 ... 163742:9849 3877:9849 3880:9849 Cell cycle control crn ... (Crooked neck) protein-like protein Medicago trunc ...

  16. Protein (Viridiplantae): 357472389 [

    Full Text Available XP_003606479.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAETSSSNN ...

  17. Protein (Viridiplantae): 357472385 [

    Full Text Available XP_003606477.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAETSSSNN ...

  18. Protein (Viridiplantae): 357440307 [

    Full Text Available XP_003590431.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAGTSSKIP ...

  19. Protein (Viridiplantae): 357444551 [

    Full Text Available XP_003592553.1 33090:29954 35493:20452 131221:20452 3193:20452 58023:15679 78536:15788 58024:157 ... 2228 163742:12813 3877:12813 3880:12813 Defects in morphology ... protein-like protein Medicago truncatula MAGTSSKIP ...

  20. C-reactive protein

    C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. It is one of a group of proteins called "acute phase reactants" that go up in response to inflammation. ...

  1. Protein (Viridiplantae): 18414878 [

    Full Text Available NP_567527.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:13546 3 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  2. Protein (Viridiplantae): 238480800 [

    Full Text Available NP_001154247.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:1354 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  3. Protein (Viridiplantae): 238480798 [

    Full Text Available NP_001154246.1 33090:1722 35493:20777 131221:20777 3193:20777 58023:13588 78536:13546 58024:1354 ... 83:5979 3701:5979 3702:6150 Tryptophan RNA-binding attenuator ... protein-like protein Arabidopsis thaliana MAAPFFST ...

  4. Protein (Cyanobacteria): 305313 [

    Full Text Available ZP_09781770.1 1117:5986 1150:1684 35823:2516 376219:684 Cytochrome b6-f complex iron -sulfur subu ... nit 1 (Rieske iron -sulfur protein 1) (Plastohydroquinone:plastocyanin ... oxidoreductase iron -sulfur protein 1) (ISP 1) (RISP 1) Arthrospira sp. ...

  5. Protein Attachment on Nanodiamonds.

    Lin, Chung-Lun; Lin, Cheng-Huang; Chang, Huan-Cheng; Su, Meng-Chih


    A recent advance in nanotechnology is the scale-up production of small and nonaggregated diamond nanoparticles suitable for biological applications. Using detonation nanodiamonds (NDs) with an average diameter of ∼4 nm as the adsorbents, we have studied the static attachment of three proteins (myoglobin, bovine serum albumin, and insulin) onto the nanoparticles by optical spectroscopy, mass spectrometry, and dynamic light scattering, and electrophoretic zeta potential measurements. Results show that the protein surface coverage is predominantly determined by the competition between protein-protein and protein-ND interactions, giving each protein a unique and characteristic structural configuration in its own complex. Specifically, both myoglobin and bovine serum albumin show a Langmuir-type adsorption behavior, forming 1:1 complexes at saturation, whereas insulin folds into a tightly bound multimer before adsorption. The markedly different adsorption patterns appear to be independent of the protein concentration and are closely related to the affinity of the individual proteins for the NDs. The present study provides a fundamental understanding for the use of NDs as a platform for nanomedical drug delivery. PMID:25815400

  6. Protein sequence databases.

    Apweiler, Rolf; Bairoch, Amos; Wu, Cathy H


    A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of further information in each sequence record. As the focus of researchers moves from the genome to the proteins encoded by it, these databases will play an even more important role as central comprehensive resources of protein information. Several the leading protein sequence databases are discussed here, with special emphasis on the databases now provided by the Universal Protein Knowledgebase (UniProt) consortium. PMID:15036160

  7. Manipulating and Visualizing Proteins

    Simon, Horst D.


    ProteinShop Gives Researchers a Hands-On Tool for Manipulating, Visualizing Protein Structures. The Human Genome Project and other biological research efforts are creating an avalanche of new data about the chemical makeup and genetic codes of living organisms. But in order to make sense of this raw data, researchers need software tools which let them explore and model data in a more intuitive fashion. With this in mind, researchers at Lawrence Berkeley National Laboratory and the University of California, Davis, have developed ProteinShop, a visualization and modeling program which allows researchers to manipulate protein structures with pinpoint control, guided in large part by their own biological and experimental instincts. Biologists have spent the last half century trying to unravel the ''protein folding problem,'' which refers to the way chains of amino acids physically fold themselves into three-dimensional proteins. This final shape, which resembles a crumpled ribbon or piece of origami, is what determines how the protein functions and translates genetic information. Understanding and modeling this geometrically complex formation is no easy matter. ProteinShop takes a given sequence of amino acids and uses visualization guides to help generate predictions about the secondary structures, identifying alpha helices and flat beta strands, and the coil regions that bind them. Once secondary structures are in place, researchers can twist and turn these pre-configurations until they come up with a number of possible tertiary structure conformations. In turn, these are fed into a computationally intensive optimization procedure that tries to find the final, three-dimensional protein structure. Most importantly, ProteinShop allows users to add human knowledge and intuition to the protein structure prediction process, thus bypassing bad configurations that would otherwise be fruitless for optimization. This saves compute cycles and accelerates

  8. MicroProteins

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz;


    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...... characteristics of a miP. In this opinion article, we clearly state the characteristics of a miP as evidenced by known proteins that fit the definition; we explain why modulatory proteins misrepresented as miPs do not qualify as true miPs. We also discuss the evolutionary history of miPs, and how the miP concept...... can extend beyond transcription factors (TFs) to encompass different non-TF proteins that require dimerization for full function....

  9. The centrality of cancer proteins in human protein-protein interaction network: a revisit.

    Xiong, Wei; Xie, Luyu; Zhou, Shuigeng; Liu, Hui; Guan, Jihong


    Topological analysis of protein-protein interaction (PPI) networks has been widely applied to the investigation on cancer mechanisms. However, there is still a debate on whether cancer proteins exhibit more topological centrality compared to the other proteins in the human PPI network. To resolve this debate, we first identified four sets of human proteins, and then mapped these proteins into the yeast PPI network by homologous genes. Finally, we compared these proteins' properties in human and yeast PPI networks. Experiments over two real datasets demonstrated that cancer proteins tend to have higher degree and smaller clustering coefficient than non-cancer proteins. Experimental results also validated that cancer proteins have larger betweenness centrality compared to the other proteins on the STRING dataset. However, on the BioGRID dataset, the average betweenness centrality of cancer proteins is larger than that of disease and control proteins, but smaller than that of essential proteins. PMID:24878726

  10. Protein oxidation in aquatic foods

    Baron, Caroline P.


    The chapter discusses general considerations about protein oxidation and reviews the mechanisms involved in protein oxidation and consequences of protein oxidation on fish proteins. It presents two case studies, the first deals with protein and lipid oxidation in frozen rainbow trout......, and the second with oxidation in salted herring. The mechanisms responsible for initiation of protein oxidation are unclear, but it is generally accepted that free radical species initiating lipid oxidation can also initiate protein oxidation. The chapter focuses on interaction between protein and lipid...... oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...

  11. An Algorithm for Finding Functional Modules and Protein Complexes in Protein-Protein Interaction Networks

    Guangyu Cui; Yu Chen; De-Shuang Huang; Kyungsook Han


    Biological processes are often performed by a group of proteins rather than by individual proteins, and proteins in a same biological group form a densely connected subgraph in a protein-protein interaction network. Therefore, finding a densely connected subgraph provides useful information to predict the function or protein complex of uncharacterized proteins in the highly connected subgraph. We have developed an efficient algorithm and program for finding cliques and near-cliques in a prote...

  12. Quantification of the Influence of Protein-Protein Interactions on Adsorbed Protein Structure and Bioactivity

    Wei, Yang; Thyparambil, Aby A.; Latour, Robert A.


    While protein-surface interactions have been widely studied, relatively little is understood at this time regarding how protein-surface interaction effects are influenced by protein-protein interactions and how these effects combine with the internal stability of a protein to influence its adsorbed-state structure and bioactivity. The objectives of this study were to develop a method to study these combined effects under widely varying protein-protein interaction conditions using hen egg-whit...

  13. New approach for predicting protein-protein interactions


    @@ Protein-protein interactions (PPIs) are of vital importance for virtually all processes of a living cell. The study of these associations of protein molecules could improve people's understanding of diseases and provide basis for therapeutic approaches.

  14. Analysis of correlations between protein complex and protein-protein interaction and mRNA expression

    CAI Lun; XUE Hong; LU Hongchao; ZHAO Yi; ZHU Xiaopeng; BU Dongbo; LING Lunjiang; CHEN Runsheng


    Protein-protein interaction is a physical interaction of two proteins in living cells. In budding yeast Saccharomyces cerevisiae, large-scale protein-protein interaction data have been obtained through high-throughput yeast two-hybrid systems (Y2H) and protein complex purification techniques based on mass-spectrometry. Here, we collect 11855 interactions between total 2617 proteins. Through seriate genome-wide mRNA expression data, similarity between two genes could be measured. Protein complex data can also be obtained publicly and can be translated to pair relationship that any two proteins can only exist in the same complex or not. Analysis of protein complex data, protein-protein interaction data and mRNA expression data can elucidate correlations between them. The results show that proteins that have interactions or similar expression patterns have a higher possibility to be in the same protein complex than randomized selected proteins, and proteins which have interactions and similar expression patterns are even more possible to exist in the same protein complex. The work indicates that comprehensive integration and analysis of public large-scale bioinformatical data, such as protein complex data, protein-protein interaction data and mRNA expression data, may help to uncover their relationships and common biological information underlying these data. The strategies described here may help to integrate and analyze other functional genomic and proteomic data, such as gene expression profiling, protein-localization mapping and large-scale phenotypic data, both in yeast and in other organisms.

  15. Piezoelectric allostery of protein.

    Ohnuki, Jun; Sato, Takato; Takano, Mitsunori


    Allostery is indispensable for a protein to work, where a locally applied stimulus is transmitted to a distant part of the molecule. While the allostery due to chemical stimuli such as ligand binding has long been studied, the growing interest in mechanobiology prompts the study of the mechanically stimulated allostery, the physical mechanism of which has not been established. By molecular dynamics simulation of a motor protein myosin, we found that a locally applied mechanical stimulus induces electrostatic potential change at distant regions, just like the piezoelectricity. This novel allosteric mechanism, "piezoelectric allostery", should be of particularly high value for mechanosensor/transducer proteins. PMID:27575163

  16. Alpha Shapes and Proteins

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  17. Protein crystallography prescreen kit

    Segelke, Brent W.; Krupka, Heike I.; Rupp, Bernhard


    A kit for prescreening protein concentration for crystallization includes a multiplicity of vials, a multiplicity of pre-selected reagents, and a multiplicity of sample plates. The reagents and a corresponding multiplicity of samples of the protein in solutions of varying concentrations are placed on sample plates. The sample plates containing the reagents and samples are incubated. After incubation the sample plates are examined to determine which of the sample concentrations are too low and which the sample concentrations are too high. The sample concentrations that are optimal for protein crystallization are selected and used.

  18. Human Protein Z.

    Broze, G J; Miletich, J P


    Protein Z was purified from human plasma by a four-step procedure which included barium citrate adsorption, ammonium sulfate fractionation, DEAE-Sepharose chromatography, and blue agarose chromatography with a yield of 20%. It is a 62,000 mol wt protein with an extinction coefficient of 12.0. The concentration of Protein Z in pooled, citrated plasma is 2.2 micrograms/ml and its half-life in patients starting warfarin anticoagulation therapy is estimated to be less than 2.5 d. The NH2-terminal...

  19. Evolution of proteins.

    Dayhoff, M. O.


    The amino acid sequences of proteins from living organisms are dealt with. The structure of proteins is first discussed; the variation in this structure from one biological group to another is illustrated by the first halves of the sequences of cytochrome c, and a phylogenetic tree is derived from the cytochrome c data. The relative geological times associated with the events of this tree are discussed. Errors which occur in the duplication of cells during the evolutionary process are examined. Particular attention is given to evolution of mutant proteins, globins, ferredoxin, and transfer ribonucleic acids (tRNA's). Finally, a general outline of biological evolution is presented.

  20. The characterisation and prediction of protein-protein interfaces.

    Kabir, T.


    Understanding how proteins interact with each other is of fundamental importance and is one of the most important goals of molecular biology. In order to study the characteristics of protein-protein interaction sites datasets of non-homologous protein-complexes have been compiled. These datasets include 142 obligate homocomplexes, 20 obligate hetero-complexes, 20 enzyme-inhibitor complexes, 15 antibody-antigen complexes, and 10 signaling complexes. Overall, the protein-protein interfaces of o...

  1. Whey Protein- The Role of Protein Supplementation in Resistance Training

    Zimmer, Raymond


    Adequate protein intake is an important concern for many athletes who are undergoing strength-training programs. Many athletes choose to take a protein supplement, such as whey protein, in order to help them build lean muscle mass more efficiently. But the benefit of very high levels of dietary protein in resistance training remains questionable. This paper examines the effectiveness of whey protein, and other forms of protein supplements, in helping athletes augment their muscle mass. A comp...

  2. Protein-protein interaction databases: keeping up with growing interactomes

    Lehne Benjamin; Schlitt Thomas


    Abstract Over the past few years, the number of known protein-protein interactions has increased substantially. To make this information more readily available, a number of publicly available databases have set out to collect and store protein-protein interaction data. Protein-protein interactions have been retrieved from six major databases, integrated and the results compared. The six databases (the Biological General Repository for Interaction Datasets [BioGRID], the Molecular INTeraction ...

  3. The effect of protein-protein and protein-membrane interactions on membrane fouling in ultrafiltration

    Huisman, I.H.; Prádanos, P.; Hernández, A.


    It was studied how protein-protein and protein-membrane interactions influence the filtration performance during the ultrafiltration of protein solutions over polymeric membranes. This was done by measuring flux, streaming potential, and protein transmission during filtration of bovine serum albumin

  4. Polymers for Protein Conjugation

    Gianfranco Pasut


    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  5. Protein (Cyanobacteria): 292092 [

    Full Text Available ZP_11392515.1 1117:5087 1150:2441 44887:135 864702:135 PAS ... domain type 3-containing protein,PAS ... STISDITSQKRTEAALQRSTARYENLASNIPGMIYQVVLETNGHFRFAYASPAS REIFGLEPEQLMKSAALGMTVIHPDDVVSFRQSIAQSAKTLQTQLGKLPK ...

  6. Protein turnover in sheep

    Considerable advances have been made in the knowledge of the mechanisms and control of synthesis and degradation of proteins in animal tissues during the last decade. Most of the work on the measurement of synthetic and degradative rates of the mixed protein fraction from tissues has been conducted in the rat. There have, unfortunately, been few publications describing results of protein turnover studies with ruminants. Consideration is given here to the techniques used to measure protein turnover, and some of the results obtained, particularly with sheep, are summarized. No attempt has been made to discuss directly the situation in parasitized animals; rather the aim is to provide background information which complements other work dealing with the effects of parasites on the nitrogen metabolism of ruminants. (author)

  7. Engineered Proteins for Bioelectrochemistry

    Akram, Muhammad Safwan; Rehman, Jawad Ur; Hall, Elizabeth A. H.


    It is only in the past two decades that excellent protein engineering tools have begun to meet parallel advances in materials chemistry, nanofabrication, and electronics. This is revealing scenarios from which synthetic enzymes can emerge, which were previously impossible, as well as interfaces with novel electrode materials. That means the control of the protein structure, electron transport pathway, and electrode surface can usher us into a new era of bioelectrochemistry. This article reviews the principle of electron transfer (ET) and considers how its application at the electrode, within the protein, and at a redox group is directing key advances in the understanding of protein structure to create systems that exhibit better efficiency and unique bioelectrochemistry.

  8. Protein (Viridiplantae): 308813231 [

    Full Text Available XP_003083922.1 33090:9527 3041:5078 1035538:3664 13792:3664 70447:4128 70448:5494 Protein requir ... ed for actin cytoskeleton organization ... and cell cycle progression (ISS) Ostreococcus taur ...

  9. Protein (Viridiplantae): 308808566 [

    Full Text Available XP_003081593.1 33090:6182 3041:4098 1035538:2508 13792:2508 70447:3211 70448:4097 Mitochondrial ... inheritance and actin cytoskeleton organization ... protein (ISS) Ostreococcus tauri MPPKKPPPPPPDAKSYP ...

  10. The Pentapeptide Repeat Proteins

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.


    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  11. Protein (Viridiplantae): 255084748 [

    Full Text Available XP_002504805.1 33090:7862 3041:6362 1035538:5159 13792:5159 38832:5340 296587:5427 DUF1244/molyb ... denum cofactor synthesis ... fusion protein Micromonas sp. RCC299 MASTRTEIEAYAF ...

  12. Protein (Viridiplantae): 303283029 [

    Full Text Available XP_003060806.1 33090:7862 3041:6362 1035538:5159 13792:5159 38832:5340 38833:5093 564608:5093 mo ... lybdenum cofactor synthesis ... protein Micromonas pusilla CCMP1545 MVDAQTTEKIEAYA ...

  13. Protein (Viridiplantae): 308812183 [

    Full Text Available XP_003083399.1 33090:12970 3041:5897 1035538:4613 13792:4613 70447:1628 70448:5196 Glycosylphosp ... hatidylinositol anchor synthesis ... protein (ISS) Ostreococcus tauri MSARRASFQSRFNDSSQ ...

  14. Protein (Viridiplantae): 308810647 [

    Full Text Available XP_003082632.1 33090:15674 3041:5296 1035538:3911 13792:3911 70447:3635 70448:4717 senescence-in ... ducible chloroplast stay-green ... protein (ISS) Ostreococcus tauri MDRATTSSRASTARTFH ...

  15. Protein (Viridiplantae): 308811905 [

    Full Text Available XP_003083260.1 33090:255 3041:4962 1035538:3528 13792:3528 70447:3840 70448:5111 T08009 probable ... ribosomal protein L5-green ... alga (ISS) Ostreococcus tauri MGKRRQKRKSQSVAKTTAYQ ...

  16. Protein (Cyanobacteria): 28423 [

    Full Text Available ZP_10226597.1 1117:517 1118:7626 1125:2051 1160279:627 Type 4 prepilin-like proteins leader ... pept ... ide-processing enzyme (Includes: Leader ... peptidase ; N-methyltransferase) Microcystis sp. T ...

  17. Protein (Cyanobacteria): 360784 [

    Full Text Available YP_007097029.1 1117:17211 1118:17546 217161:1718 1173032:1718 1173020:1718 putative stress ... prote ... in (general stress ... protein 26) Chamaesiphon minutus PCC 6605 MANATENQ ...

  18. Protein (Cyanobacteria): 392180 [

    Full Text Available ZP_07113914.1 1117:24513 1150:7038 1158:3915 272129:3709 Bifunctional protein birA (Includes: Biotin ... otin operon repressor; Biotin --(acetyl-CoA-carboxylase) synthetase (Biotin --prot ...

  19. Interactive protein manipulation


    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures.

  20. Protein (Viridiplantae): 308811366 [

    Full Text Available XP_003082991.1 33090:1951 3041:1340 1035538:592 13792:592 70447:610 70448:205 Transporter, ABC s ... uperfamily (Breast cancer ... resistance protein) (ISS), partial Ostreococcus ta ...

  1. Protein (Viridiplantae): 308810513 [

    Full Text Available XP_003082565.1 33090:8864 3041:8803 1035538:7822 13792:7822 70447:3615 70448:4680 Predicted memb ... rane protein (associated with esophageal cancer ... in humans) (ISS) Ostreococcus tauri MTSSRKLCAFVRDA ...

  2. Protein (Viridiplantae): 308804289 [

    Full Text Available XP_003079457.1 33090:1951 3041:1340 1035538:592 13792:592 70447:610 70448:205 Transporter, ABC s ... uperfamily (Breast cancer ... resistance protein) (ISS) Ostreococcus tauri MASRV ...

  3. Untying knots in proteins.

    Sułkowska, Joanna I; Sułkowski, Piotr; Szymczak, Piotr; Cieplak, Marek


    A shoelace can be readily untied by pulling its ends rather than its loops. Attempting to untie a native knot in a protein can also succeed or fail depending on where one pulls. However, thermal fluctuations induced by the surrounding water affect conformations stochastically and may add to the uncertainty of the outcome. When the protein is pulled by the termini, the knot can only get tightened, and any attempt at untying results in failure. We show that, by pulling specific amino acids, one may easily retract a terminal segment of the backbone from the knotting loop and untangle the knot. At still other amino acids, the outcome of pulling can go either way. We study the dependence of the untying probability on the way the protein is grasped, the pulling speed, and the temperature. Elucidation of the mechanisms underlying this dependence is critical for a successful experimental realization of protein knot untying. PMID:20857930

  4. Protein (Viridiplantae): 308806666 [

    Full Text Available XP_003080644.1 33090:21099 3041:5360 1035538:3986 13792:3986 70447:3049 70448:3532 COG3310: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MRRTCASRNLARSPVAARERCRQMV ...

  5. Protein (Viridiplantae): 308803575 [

    Full Text Available XP_003079100.1 33090:20519 3041:4460 1035538:2940 13792:2940 70447:2035 70448:2555 COG4399: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MKALQRLVLRGSTDGVRPACERAMA ...

  6. Protein (Viridiplantae): 308804123 [

    Full Text Available XP_003079374.1 33090:20519 3041:4460 1035538:2940 13792:2940 70447:2035 70448:2555 COG4399: Unch ... aracterized protein conserved in bacteria ... (ISS) Ostreococcus tauri MDSLATSRRRRLARAGAAIATALAL ...

  7. Protein (Viridiplantae): 255077633 [

    Full Text Available XP_002502450.1 33090:20956 3041:5145 1035538:3740 13792:3740 38832:3722 296587:3525 isocitrate d ... ehydrogenase (NADP+), bacteria -like protein Micromonas sp. RCC299 MAAASAGGKIQAAPM ...

  8. Protein (Cyanobacteria): 228257 [

    Full Text Available ZP_09784859.1 1117:4333 1150:1533 35823:3512 376219:3411 Protein ushA precursor (Includes: UDP-sugar ... ugar hydrolase (UDP-sugar ... pyrophosphatase) (UDP-sugar ... diphosphatase); 5'-nuc ...

  9. Protein folding and cosmology

    González-Diáz, P F


    Protein denaturing induced by supercooling is interpreted as a process where some or all internal symmetries of the native protein are spontaneously broken. Hence, the free-energy potential corresponding to a folding-funnel landscape becomes temperature-dependent and describes a phase transition. The idea that deformed vortices could be produced in the transition induced by temperature quenching, from native proteins to unfolded conformations is discussed in terms of the Zurek mechanism that implements the analogy between vortices, created in the laboratory at low energy, and the cosmic strings which are thought to have been left after symmetry breaking phase transitions in the early universe. An experiment is proposed to test the above idea which generalizes the cosmological analogy to also encompass biological systems and push a step ahead the view that protein folding is a biological equivalent of the big bang.

  10. Protein (Viridiplantae): 308804764 [

    Full Text Available XP_003079694.1 33090:24290 3041:9393 1035538:8433 13792:8433 70447:5209 70448:2928 probable memb ... rane protein YCR013c-yeast ... (ISS) Ostreococcus tauri MQLREVKERLRAYFSSSAATPGRTR ...