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https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#1
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28229972/early-life-stress-experience-may-blunt-hypothalamic-leptin-signalling
#2
J H Lee, S B Yoo, J Y Kim, J Y Lee, B T Kim, K Park, J W Jahng
The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229915/regulated-methionine-oxidation-by-monooxygenases
#3
REVIEW
Bruno Manta, Vadim N Gladyshev
Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant...
February 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28229387/the-effects-of-cerium-valence-states-at-cerium-oxide-coatings-on-the-responses-of-bone-mesenchymal-stem-cells-and-macrophages
#4
Mingyu You, Kai Li, Youtao Xie, Liping Huang, Xuebin Zheng
Ideal orthopedic coatings should trigger good osteogenic response and limited inflammatory response. The cerium valence states in ceria are associated with their anti-oxidative activity and anti-inflammatory property. In the study, we prepared two kinds of plasma sprayed CeO2 coatings with different Ce(4+) concentrations to investigate the effects of Ce valence states on the response of bone mesenchymal stem cells (BMSCs) and macrophage RAW264.7. Both the coatings (CeO2-A and CeO2-B) were characterized via XRD, SEM, and X-ray photoelectron spectroscopy...
February 22, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28228214/inhibition-of-protein-tyrosine-phosphatase-non-receptor-type-2-by-ptp-inhibitor-xix-its-role-as-a-multiphosphatase-inhibitor
#5
Hien Thi Thu Le, Young-Chang Cho, Sayeon Cho
Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2...
February 23, 2017: BMB Reports
https://www.readbyqxmd.com/read/28228082/recent-advances-in-protein-tyrosine-phosphatase-1b-targeted-drug-discovery-for-type-ii-diabetes-and-obesity
#6
Neelesh Maheswari, Chandrabose Karthikeyan, Piyush Trivedi, N S Hari Narayana Moorthy
Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for type II diabetes and obesity because of its pivotal role as a negative modulator in both insulin and leptin signalling pathways. Consequently, the discovery of PTP1B inhibitors has been the focus of researchers in both academia and pharmaceutical industry over the last two decades. Though, intense pharmaceutical research in this area has resulted in many potent PTP1B inhibitors, a vast majority of them possessed pTyr mimetic group such as phosphonates, carboxylic acids and sulphamic acids, which led to poor PTP1B selectivity and insufficient in vivo efficacy due to low cell permeability and bioavailability...
February 22, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28224917/regulation-of-the-wheat-map-kinase-phosphatase-1-by-14-3-3-proteins
#7
Mouna Ghorbel, Valérie Cotelle, Chantal Ebel, Ikram Zaidi, Mélanie Ormancey, Jean-Philippe Galaud, Moez Hanin
Plant MAP kinase phosphatases (MKPs) are major regulators of MAPK signaling pathways and play crucial roles in controlling growth, development and stress responses. The presence of several functional domains in plant MKPs such as a dual specificity phosphatase catalytic domain, gelsolin, calmodulin-binding and serine-rich domains, suggests that MKPs can interact with distinct cellular partners, others than MAPKs. In this report, we identified a canonical mode I 14-3-3-binding motif (574KLPSLP579) located at the carboxy-terminal region of the wheat MKP, TMKP1...
April 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28224609/mir-181-elevates-akt-signaling-by-co-targeting-phlpp2-and-inpp4b-phosphatases-in-luminal-breast-cancer
#8
Michaela Strotbek, Simone Schmid, Ismael Sànchez-Gonzàlez, Melanie Boerries, Hauke Busch, Monilola A Olayioye
The PI3K-Akt pathway is one of the most commonly dysregulated cancer-associated signaling pathways. Here we report an oncogenic function for the miR-181 family in luminal breast cancer cells that involves Akt hyperactivation. We show that miR-181a and miR-181d post-transcriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation. Ectopic expression of miR-181a and miR-181d promoted S-phase entry and cell proliferation, which was reversed by pharmacological Akt inhibition...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224476/protein-phosphatase-2a-a-double-faced-phosphatase-of-cellular-system-and-its-role-in-neurodegenerative-disorders
#9
REVIEW
Md Nematullah, M N Hoda, Farah Khan
Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, is a vitally important phosphatase for the cellular system. Structurally, it is constituted of three different subunits, namely catalytic subunit (PP2Ac), structural scaffold subunit (PP2A-A), and regulatory subunit (PP2A-B). All subunits have various isoforms, and catalytic and scaffold subunits are ubiquitously expressed, whereas regulatory subunits are more specific to tissue and cell type. It is the numerous possibilities of PP2A holoenzyme assembly with varying isoform components that make it possess a dual nature of activator or the inhibitory character in different signaling pathways, namely neural developmental pathways, Akt/protein kinase B pathway, NF-kB pathway, MAPK pathway, apoptosis pathway, and cell cycle progression to name a few...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28223411/pentraxin-3-is-a-pi3k-signaling-target-that-promotes-stem-cell-like-traits-in-basal-like-breast-cancers
#10
Clémence Thomas, Whitney Henry, Benjamin G Cuiffo, Anthony Y Collmann, Elisabetta Marangoni, Vanessa Benhamo, Manoj K Bhasin, Cheng Fan, Laetitia Fuhrmann, Albert S Baldwin, Charles Perou, Anne Vincent-Salomon, Alex Toker, Antoine E Karnoub
Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics...
February 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28223368/phosphatases-generate-signal-specificity-downstream-of-ssp1-kinase-in-fission-yeast
#11
Lin Deng, Mid Eum Lee, Katherine Schutt, James B Moseley
AMPK-related protein kinases (ARKs) coordinate cell growth, proliferation, and migration with environmental status. It is unclear how specific ARKs are activated at specific times. In fission yeast S. pombe, the CaMKK-like protein kinase Ssp1 promotes cell cycle progression by activating the ARK Cdr2 according to cell growth signals. Here, we demonstrate that Ssp1 activates a second ARK, Ssp2/AMPK-α, for cell proliferation in low environmental glucose. Ssp1 activates these two related targets by the same biochemical mechanism: direct phosphorylation of a conserved residue in the activation loop (Cdr2-T166 and Ssp2-T189)...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28223354/il-1%C3%AE-induced-and-p38-mapk-dependent-activation-of-the-mitogen-activated-protein-kinase-mapk-activated-protein-kinase-mk-2-in-hepatocytes-signal-transduction-with-robust-and-concentration-independent-signal-amplification
#12
Andreas Kulawik, Raphael Engesser, Christian Ehlting, Andreas Raue, Ute Albrecht, Bettina Hahn, Wolf-Dieter Lehmann, Matthias Gaestel, Ursula Klingmüller, Dieter Häussinger, Jens Timmer, Johannes G Bode
The Interleukin (IL)-1β induced activation of the p38(MAPK)/MK2 pathway in hepatocytes is important for the control of acute phase response and regulation of liver regeneration. Many aspects of regulatory relevance of this pathway have been investigated in immune cells in the context of inflammation. However, very little is known about concentration-dependent activation kinetics and signal propagation in hepatocytes and the role of MK2. We established a mathematical model for IL-1β induced activation of the p38(MAPK)/MK2 pathway in hepatocytes that was calibrated to quantitative data on time- and IL-1β concentration-dependent phosphorylation of p38(MAPK) and MK2 in primary mouse hepatocytes...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28222767/knockdown-of-slc41a1-magnesium-transporter-promotes-mineralization-and-attenuates-magnesium-inhibition-during-osteogenesis-of-mesenchymal-stromal-cells
#13
Yu-Tzu Tsao, Ya-Yi Shih, Yu-An Liu, Yi-Shiuan Liu, Oscar K Lee
BACKGROUND: Magnesium is essential for numerous physiological functions. Magnesium exists mostly in bone and the amount is dynamically regulated by skeletal remodeling. Accelerating bone mass loss occurs when magnesium intake is insufficient; whereas high magnesium could lead to mineralization defects. However, the underlying magnesium regulatory mechanisms remain elusive. In the present study, we investigated the effects of high extracellular magnesium concentration on osteogenic differentiation of mesenchymal stromal/stem cells (MSCs) and the role of magnesium transporter SLC41A1 in the mineralization process...
February 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28222387/baicalein-enhances-the-osteogenic-differentiation-of-human-periodontal-ligament-cells-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#14
Li-Jiao Chen, Bi-Bo Hu, Xin-Lian Shi, Man-Man Ren, Wen-Bin Yu, Sheng-Dan Cen, Rong-Dang Hu, Hui Deng
OBJECTIVE: Periodontium regeneration is one of the most important processes for periodontitis therapy. Human periodontal ligament cells (hPDLCs) play a vital role in the repair and regeneration of periodontal tissues. Our study aimed to investigated the mechanisms underlying the promotion of hPLDCs osteogenic differentiation by baicalein. DESIGN: hPDLCs were obtained from periodontal ligament (PDL) tissues by primary culture. The MTT assay was used to determine the growth curves of hPDLCs treated with different concentrations of baicalein (1...
February 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28222153/dissecting-nutrient-related-co-expression-networks-in-phosphate-starved-poplars
#15
Mareike Kavka, Andrea Polle
Phosphorus (P) is an essential plant nutrient, but its availability is often limited in soil. Here, we studied changes in the transcriptome and in nutrient element concentrations in leaves and roots of poplars (Populus × canescens) in response to P deficiency. P starvation resulted in decreased concentrations of S and major cations (K, Mg, Ca), in increased concentrations of N, Zn and Al, while C, Fe and Mn were only little affected. In roots and leaves >4,000 and >9,000 genes were differently expressed upon P starvation...
2017: PloS One
https://www.readbyqxmd.com/read/28220141/adhesive-peptide-sequences-regulate-valve-interstitial-cell-adhesion-phenotype-and-extracellular-matrix-deposition
#16
Yan Wu, K Jane Grande-Allen, Jennifer L West
Knowledge of how extracellular matrix (ECM) binding impacts valve interstitial cells (VICs) is critical not only to better understanding the etiology of valvular diseases but also to constructing living valve substitutes that can grow and remodel. Use of ECM-mimicking adhesive peptides with specific affinity to different receptors provides insights into adhesion-mediated cell signaling and downstream outcomes. Expression of adhesion receptors by VICs was assessed by flow cytometry and used to guide the choice of peptides studied...
December 2016: Cellular and Molecular Bioengineering
https://www.readbyqxmd.com/read/28220078/inhibition-of-vegfr2-activation-and-its-downstream-signaling-to-erk1-2-and-calcium-by-thrombospondin-1-tsp1-in-silico-investigation
#17
Hojjat Bazzazi, Jeffery S Isenberg, Aleksander S Popel
VEGF signaling through VEGFR2 is a central regulator of the angiogenic response. Inhibition of VEGF signaling by the stress-induced matricellular protein TSP1 plays a role in modulating the angiogenic response to VEGF in both health and disease. TSP1 binding to CD47 inhibits VEGFR2 activation. The full implications of this inhibitory interaction are unknown. We developed a detailed rule-based computational model to inquire if TSP1-CD47 signaling through VEGF had downstream effects upon ERK1/2 and calcium. Our Simulations suggest that enhanced degradation of VEGFR2 initiated by the binding of TSP1 to CD47 is sufficient to explain the inhibition of VEGFR2 phosphorylation, calcium elevation, and ERK1/2 activation downstream of VEGF...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28219249/enhanced-photoelectrochemical-method-for-sensitive-detection-of-protein-kinase-a-activity-using-tio2-g-c3n4-pamam-dendrimer-and-alkaline-phosphatase
#18
Xue Li, Lusheng Zhu, Yunlei Zhou, Huanshun Yin, Shiyun Ai
A novel photoelectrochemical (PEC) assay is developed for sensitive detection of protein kinase A (PKA) activity based on PKA-catalyzed phosphorylation reaction in solution and signal amplification strategy triggered by PAMAM dendrimer and alkaline phosphatase (ALP). In this strategy, it is noteworthy at this point that PKA phosphorylation was achieved in solution instead of on the surface of the electrode, which has advantages of the good contact in reactants and simple experimental procedure. For immobilizing the phosphorylated peptide (P-peptide) on electrode surface, graphite-like carbon nitride (g-C3N4) and titanium dioxide (TiO2) complex is synthesized and characterized, which plays a significant role for TiO2 conjugating phosphate groups and g-C3N4 providing PEC signal...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28218482/osteoblastic-differentiation-of-periodontal-ligament-stem-cells-on-non-stoichiometric-calcium-phosphate-and-titanium-surfaces
#19
L Winning, L Robinson, A R Boyd, I A El Karim, F T Lundy, B J Meenan
Bioactive materials offer particular clinical benefits in the field of dental implantology, where differentiation of stem cells towards an osteoblastic lineage is required for osseointegration and appropriate function of implants in vivo. The aim of this study was to evaluate the osteoblastic response of Stro-1+ve periodontal ligament stem cells (PDLSCs) to three well-characterised biomaterial surfaces: an abraded titanium surface (cpTi) control; a polycrystalline titanium surface, with both micro and nano-topography produced by radio frequency magnetron sputtering (TiTi); and the same surface incorporating a sputter deposited calcium phosphate coating (CaP-TiTi)...
February 20, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28218391/mapk3-1-participates-in-the-activation-of-primordial-follicles-through-mtorc1-kitl-signaling
#20
Yu Zhao, Yu Zhang, Jia Li, Nana Zheng, Xiaoting Xu, Jing Yang, Guoliang Xia, Meijia Zhang
The majority of ovarian primordial follicles are preserved in a dormant state to maintain the female reproductive lifespan, and only a few primordial follicles are activated to enter the growing follicle pool in each wave. Recent studies have shown that primordial follicular activation depends on mammalian target of rapamycin complex 1 (mTORC1)-KIT ligand (KITL) signaling in pre-granulosa cells and its receptor (KIT)-phosphoinositol 3 kinase (PI3K) signaling in oocytes. However, the upstream regulator of mTORC1 signaling is unclear...
February 20, 2017: Journal of Cellular Physiology
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