BACKGROUND: Reactive oxygen species, such as superoxide (O(2)(-)), are involved in the abnormal growth of various cell types. Angiotensin II (Ang II) is one of the most potent inducers of oxidative stress in the vasculature. The molecular events involved in Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) are ... More
Involvement of c-Src Tyrosine Kinase Upstream of Class I Phosphatidylinositol (PI) 3-Kinases in Salmonella Enteritidis Rck Protein-mediated Invasion.
AuthorsWiedemann A, Rosselin M, Mijouin L, Bottreau E, Velge P,
JournalJ Biol Chem
PubMed ID22810232
'The Salmonella outer membrane protein Rck mediates a Zipper entry mechanism controlled by tyrosine phosphorylation and class I phosphatidylinositol 3-kinase (PI 3-kinase). However, the underlying mechanism leading to this signaling cascade remains unclear. The present study showed that using Rck-coated beads or Rck-overexpressing Escherichia coli, Rck-mediated actin polymerization and invasion ... More
Structural and energetic characteristics of the heparin-binding site in antithrombotic protein C.
AuthorsFriedrich U, Blom AM, Dahlbäck B, Villoutreix BO,
JournalJ Biol Chem
PubMed ID11316800
'Human activated protein C (APC) is a key component of a natural anticoagulant system that regulates blood coagulation. In vivo, the catalytic activity of APC is regulated by two serpins, alpha1-antitrypsin and the protein C inhibitor (PCI), the inhibition by the latter being stimulated by heparin. We have identified a ... More
Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells: protective role in apoptosis.
'Hypoxia is a common environmental stress that influences signaling pathways and cell function. Several cell types, including neuroendocrine chromaffin cells, have evolved to sense oxygen levels and initiate specific adaptive responses to hypoxia. Here we report that under hypoxic conditions, rat pheochromocytoma PC12 cells are resistant to apoptosis induced by ... More
Electrophoretic profiling of both RNA and protein from a single 250-pL sample.
Authors Zabzdyr Jennifer L; Lillard Sheri J;
JournalAnal Chem
PubMed ID11985318
'A novel approach is described that uses capillary electrophoresis (CE) to electrophoretically sample and separate both protein and RNA from a single injected plug of cell lysate. A 250-pL sample of lysate from Chinese hamster ovary cells (9.6 x 10(7) cells/mL) was hydrodynamically injected into a capillary containing a Tris-based ... More
Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein.
AuthorsElomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J,
JournalHum Mol Genet
PubMed ID11309369
'Anhidrotic ectodermal dysplasia (EDA) is an X-linked disorder characterized by abnormal development of ectoderm and its appendices. The EDA gene encodes different isoforms of ectodysplasin, a transmembrane protein. The two longest isoforms, ectodysplasin-A1 and -A2, which differ by an insertion of two amino acids, are trimeric type II membrane proteins ... More
Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O.
AuthorsWalev I, Bhakdi SC, Hofmann F, Djonder N, Valeva A, Aktories K, Bhakdi S,
JournalProc Natl Acad Sci U S A
PubMed ID11248053
'The pore-forming toxin streptolysin O (SLO) can be used to reversibly permeabilize adherent and nonadherent cells, allowing delivery of molecules with up to 100 kDa mass to the cytosol. Using FITC-labeled albumin, 10(5)-10(6) molecules were estimated to be entrapped per cell. Repair of toxin lesions depended on Ca(2+)-calmodulin and on ... More
Fibrin inhibits peripheral nerve remyelination by regulating schwann cell differentiation.
'Remyelination is a critical step for functional nerve regeneration. Here we show that fibrin deposition in the peripheral nervous system after injury is a key regulator of remyelination. After sciatic nerve crush, fibrin is deposited and its clearance correlates with remyelination. Fibrin induces phosphorylation of ERK1/2 and production of p75 ... More
Molecular rearrangements of the extracellular vestibule in NMDAR channels during gating.
Authors Sobolevsky Alexander I; Beck Christine; Wollmuth Lonnie P;
JournalNeuron
PubMed ID11779481
Many N-methyl-D-aspartate receptor (NMDAR) channel blockers that have therapeutic potential can be trapped in the closed state. Using a combination of the substituted cysteine accessibility method and open channel blockers, we found that the M3 segment forms the core of the extracellular vestibule, including a deep site for trapping blockers. ... More
Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores.
AuthorsSharma G, Vijayaraghavan S,
JournalProc Natl Acad Sci U S A
PubMed ID11259680
In this report we provide evidence that neuronal nicotinic acetylcholine receptors (nAChRs) are present on hippocampal astrocytes and their activation produces rapid currents and calcium transients. Our data indicate that these responses obtained from astrocytes are primarily mediated by an AChR subtype that is functionally blocked by alpha-bungarotoxin (alpha Bgt) ... More
Chemical synthesis and biological activity of bromohydrin pyrophosphate, a potent stimulator of human gamma delta T cells.
Small phosphorylated metabolites from mycobacteria stimulate human gammadelta T lymphocytes. Although such phosphoantigens could prove useful in the composition of vaccines involving gammadelta T cell-mediated immunity, their very low abundance in natural sources limits such applications. Here, we describe the chemical production, purification, and bioactivity of a phosphorylated bromohydrin (BrHPP) ... More
Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7.
AuthorsArdley HC, Tan NG, Rose SA, Markham AF, Robinson PA,
JournalJ Biol Chem
PubMed ID11278816
We recently reported the identification of a RING finger-containing protein, HHARI (human homologue of Drosophila ariadne), which binds to the human ubiquitin-conjugating enzyme UbcH7 in vitro. We now demonstrate that HHARI interacts and co-localizes with UbcH7 in mammalian cells, particularly in the perinuclear region. We have further defined a minimal ... More
Polycystin-1, the product of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells.
AuthorsScheffers MS, van der Bent P, Prins F, Spruit L, Breuning MH, Litvinov SV, de Heer E, Peters DJ,
JournalHum Mol Genet
PubMed ID11063733
Polycystin-1 is a novel protein predicted to be a large membrane-spanning glycoprotein with an extracellular N-terminus and an intracellular C-terminus, harboring several structural motifs. To study the subcellular localization, antibodies raised against various domains of polycystin-1 and against specific adhesion complex proteins were used for two-color immunofluorescence staining. In Madine ... More
High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening.
AuthorsO'Brien PJ, Irwin W, Diaz D, Howard-Cofield E, Krejsa CM, Slaughter MR, Gao B, Kaludercic N, Angeline A, Bernardi P, Brain P, Hougham C,
JournalArch Toxicol
PubMed ID16598496
To develop and validate a practical, in vitro, cell-based model to assess human hepatotoxicity potential of drugs, we used the new technology of high content screening (HCS) and a novel combination of critical model features, including (1) use of live, human hepatocytes with drug metabolism capability, (2) preincubation of cells ... More
Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis.
Authors Huang Chi-Ying F; Wu Yi-Mi; Hsu Chiung-Yueh; Lee Wan-Shu; Lai Ming-Derg; Lu Te-Jung; Huang Chia-Lin; Leu Tzeng-Horng; Shih Hsiu-Ming; Fang Hsin-I; Robinson Dan R; Kung Hsing-Jien; Yuan Chiun-Jye;
JournalJ Biol Chem
PubMed ID12107159
Mammalian Sterile 20-like kinase 3 (Mst3), the physiological functions of which are unknown, is a member of the germinal center kinase-III family. It contains a conserved kinase domain at its NH(2) terminus, whereas there is a regulatory domain at its COOH terminus. In this study we demonstrate that endogenous Mst3 ... More
Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device.
Authors Yang Mengsu; Li Cheuk-Wing; Yang Jun;
JournalAnal Chem
PubMed ID12199565
We have developed a microfluidic device for on-chip monitoring of cellular reactions. The device consists of two primary analytical functions: control of cell transport and immobilization, and dilution of an analyte solution to generate a concentration gradient. In this device, a dam structure in parallel to the fluid flow was ... More
Glycogen synthase kinase 3beta is activated by cAMP and plays an active role in the regulation of melanogenesis.
In human and mouse, cAMP plays a key role in the control of pigmentation. cAMP, through the activation of protein kinase A, increases the expression of microphthalmia-associated transcription factor (MITF), which in turn stimulates tyrosinase gene expression, to allow melanin synthesis. Beyond this simplified scheme, cAMP inhibits phosphatidylinositol 3-kinase (PI3K), ... More
Influence of second and third cytoplasmic loops on binding, internalization, and coupling of chimeric bombesin/m3 muscarinic receptors.
Authors Tseng M J; Coon S; Stuenkel E; Struk V; Logsdon C D;
JournalJ Biol Chem
PubMed ID7629092
In order to investigate the molecular basis for differences in the characteristics of bombesin (Bn) and m3 muscarinic cholinergic (m3 ACh) receptors, chimeric Bn receptors possessing cytoplasmic domains from the m3 ACh receptor were produced. The receptors were expressed in CHO-K1 cells and binding, structural, and signal transduction characteristics were ... More
CD40-mediated Activation of NF-kappa B in Airway Epithelial Cells.
Authors Propst Stacie M; Estell Kim; Schwiebert Lisa M;
JournalJ Biol Chem
PubMed ID12122011
We have reported previously that airway epithelial cells (AEC) express CD40 and that activation of this molecule stimulates the expression of inflammatory mediators, including the chemokine RANTES (regulated on activation normal T cell expressed and secreted). Because NF-kappaB regulates the expression of many inflammatory mediators, such as RANTES, we utilized ... More
Malignant effusions and immunogenic tumour-derived exosomes.
BACKGROUND: Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supernatants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with ... More
Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.
Authors Ho Ling-Pei; Davis Margaret; Denison Alan; Wood Fraser T; Greening Andrew P;
JournalChest
PubMed ID12006423
STUDY OBJECTIVES: To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis. SETTING: University teaching hospital. Patients and methods: IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with ... More
Brief exposure to high-dose transforming growth factor-beta1 enhances periosteal chondrogenesis in vitro: a preliminary report.
BACKGROUND: Articular cartilage has limited potential for repair. There have been various attempts aimed at improving the repair process in articular cartilage. Transforming growth factor-beta1 (TGF-beta1) has a stimulatory effect on chondrogenesis in periosteal explants. The purpose of the present study was to determine the effect of brief exposures (i.e., ... More
A 2-D liquid separations/mass mapping method for interlysate comparison of ovarian cancers.
Authors Kachman Maureen T; Wang Haixing; Schwartz Donald R; Cho Kathleen R; Lubman David M;
JournalAnal Chem
PubMed ID11985308
A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric ... More
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.
Authors Black Gillian F; Weir Rosemary E; Floyd Sian; Bliss Lyn; Warndorff David K; Crampin Amelia C; Ngwira Bagrey; Sichali Lifted; Nazareth Bernadette; Blackwell Jenefer M; Branson Keith; Chaguluka Steven D; Donovan Linda; Jarman Elizabeth; King Elizabeth; Fine Paul E M; Dockrell Hazel M;
JournalLancet
PubMed ID11978337
BACKGROUND: The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations. METHODS: 483 adolescents ... More
Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture.
AuthorsDaum R, Visser D, Wild C, Kutuzova L, Schneider M, Lorenz G, Weiss M, Hinderer S, Stock UA, Seifert M, Schenke-Layland K
JournalCells
PubMed ID32210018
'Appropriate mechanical properties and fast endothelialization of synthetic grafts are key to ensure long-term functionality of implants. We used a newly developed biostable polyurethane elastomer (TPCU) to engineer electrospun vascular scaffolds with promising mechanical properties (E-modulus: 4.8 ± 0.6 MPa, burst pressure: 3326 ± 78 mmHg), which were biofunctionalized with ... More
The effects of tramadol on cancer stem cells and metabolic changes in colon carcinoma cells lines.
AuthorsÖzgürbüz U, Gencür S, Kurt FÖ, Özkalkanli M, Vatansever HS
JournalGene
PubMed ID31390540
'Opioids are widely used in the treatment of cancer related pain. They mainly exert their effects on opioid receptors. The most common opioid in the treatment of pain is morphine. Previous studies show that they may have effects on cancer cell behavior. These may include apoptosis, angiogenesis, invasion, inflammation and ... More
Cholesterol Depletion Regulates Axonal Growth and Enhances Central and Peripheral Nerve Regeneration.
AuthorsRoselló-Busquets C, de la Oliva N, Martínez-Mármol R, Hernaiz-Llorens M, Pascual M, Muhaisen A, Navarro X, Del Valle J, Soriano E
JournalFront Cell Neurosci
PubMed ID30809129
'Axonal growth during normal development and axonal regeneration rely on the action of many receptor signaling systems and complexes, most of them located in specialized raft membrane microdomains with a precise lipid composition. Cholesterol is a component of membrane rafts and the integrity of these structures depends on the concentrations ... More
Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs.
AuthorsChristmas BJ, Rafie CI, Hopkins AC, Scott BA, Ma HS, Cruz KA, Woolman S, Armstrong TD, Connolly RM, Azad NA, Jaffee EM, Roussos Torres ET
JournalCancer Immunol Res
PubMed ID30341213
'Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. ... More
Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats.
AuthorsZhang Q, Nguyen PD, Shi S, Burrell JC, Xu Q, Cullen KD, Le AD
JournalMol Neurobiol
PubMed ID29372546
'Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs) is promising for potential cell-based therapies for post-traumatic peripheral nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem cells (GMSCs) could be reproducibly and readily induced into NCSCs via non-genetic approaches. Compared to parental GMSCs, induced NCSC population ... More
Diabetic Vascular Calcification Mediated by the Collagen Receptor Discoidin Domain Receptor 1 via the Phosphoinositide 3-Kinase/Akt/Runt-Related Transcription Factor 2 Signaling Axis.
AuthorsLino M, Wan MH, Rocca AS, Ngai D, Shobeiri N, Hou G, Ge C, Franceschi RT, Bendeck MP
JournalArterioscler Thromb Vasc Biol
PubMed ID29930002
'Objective- Vascular calcification is a common and severe complication in patients with atherosclerosis which is exacerbated by type 2 diabetes mellitus. Our laboratory recently reported that the collagen receptor discoidin domain receptor 1 (DDR1) mediates vascular calcification in atherosclerosis; however, the underlying mechanisms are unknown. During calcification, vascular smooth muscle ... More
l-Citrulline Metabolism in Mice Augments CD4
AuthorsLange SM, McKell MC, Schmidt SM, Hossfeld AP, Chaturvedi V, Kinder JM, McAlees JW, Lewkowich IP, Way SS, Turner J, Qualls JE
JournalFront Immunol
PubMed ID29201027
Activation, recruitment, and effector function of T lymphocytes are essential for control of mycobacterial infection. These processes are tightly regulated in T cells by the availability of l-arginine within the microenvironment. In turn, mycobacterial infection dampens T cell responsiveness through arginase induction in myeloid cells, promoting sequestration of l-arginine within ... More
Human Dental Pulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain.
AuthorsLuzuriaga J, Pastor-Alonso O, Encinas JM, Unda F, Ibarretxe G, Pineda JR
JournalFront Physiol
PubMed ID30984027
Dental pulp stem cells (DPSCs) have the capacity to give rise to cells with neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult genetically unmodified human DPSCs cultured in Neurocult ... More
Altered expression of CSF3R splice variants impacts signal response and is associated with SRSF2 mutations.
AuthorsLance A, Druhan LJ, Vestal CG, Steuerwald NM, Hamilton A, Smith M, Price A, Tjaden E, Fox AN, Avalos BR
JournalLeukemia
PubMed ID31462738
Three annotated CSF3R mRNA splice variants have been described. CSF3R-V1 is the wild-type receptor, while CSF3R-V4 is a truncated form increased in some patients with AML. CSF3R-V3 mRNA was identified in placenta more than 20 years ago, but remains largely uncharacterized due to the lack of a suitable detection assay. ... More
p62 is Negatively Implicated in the TRAF6-BECN1 Signaling Axis for Autophagy Activation and Cancer Progression by Toll-Like Receptor 4 (TLR4).
AuthorsKim MJ, Min Y, Im JS, Son J, Lee JS, Lee KY
JournalCells
PubMed ID32384667
Toll-like receptors (TLRs) induce the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) and autophagy through the TNF (Tumor necrosis factor) receptor-associated factor 6 (TRAF6)-evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) and TRAF6-BECN1 signaling axes, respectively. Having shown that p62 negatively regulates Toll-like receptor 4 (TLR4)-mediated signaling ... More