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https://www.readbyqxmd.com/read/28297665/mitotic-phosphorylation-of-trex1-c-terminus-disrupts-trex1-regulation-of-the-oligosaccharyltransferase-complex
#1
Martin Kucej, Charles S Fermaintt, Kun Yang, Ricardo A Irizarry-Caro, Nan Yan
TREX1 mutations are associated with several autoimmune and inflammatory diseases. The N-terminal DNase domain of TREX1 is important for preventing self-DNA from activating the interferon response. The C terminus of TREX1 is required for ER localization and regulation of oligosacchariyltransferase (OST) activity. Here, we show that during mitosis TREX1 is predominately phosphorylated at the C-terminal Serine-261 by Cyclin B/CDK1. TREX1 is dephosphorylated quickly at mitotic exit, likely by PP1/PP2-type serine/threonine phosphatase...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28294316/knockout-of-atg5-leads-to-malignant-cell-transformation-and-resistance-to-src-family-kinase-inhibitor-pp2
#2
Sung-Hee Hwang, Byeal-I Han, Michael Lee
Autophagy can either promote or inhibit cell death in different cellular contexts. In this study, we investigated the role of autophagy in ATG5 knockout (KO) cell line established using CRISPR/Cas9 system. In ATG5 KO cells, RT-PCR and immunoblot of LC3 confirmed the functional gene knockout. We found that knockout of ATG5 significantly increased proliferation of NIH 3T3 cells. In particular, autophagy deficiency enhanced susceptibility to cellular transformation as determined by an in vitro clonogenic survival assay and a soft agar colony formation assay...
March 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28281075/concentration-dependent-alterations-in-gene-expression-induced-by-cadmium-in-solanum-lycopersicum
#3
Jing Hou, Xinhui Liu, Baoshan Cui, Junhong Bai, Xiangke Wang
Cadmium (Cd) toxicity in agricultural soil has received significant attention because of its higher transformation in the food chain and toxicity to humans. The aim of the present study was to develop sensitive and specific biomarkers for Cd stress. Therefore, transcriptional analyses were performed to investigate concentration-response characteristics of Cd responsive genes identified from a Solanum lycopersicum microarray. The results showed that the lowest observable adverse effect concentrations (LOAECs) of Cd to S...
March 10, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28280420/chronic-ca-2-influx-through-voltage-dependent-ca-2-channels-enhance-delayed-rectifier-k-currents-via-activating-src-family-tyrosine-kinase-in-rat-hippocampal-neurons
#4
Yoon-Sil Yang, Sang-Chan Jeon, Dong-Kwan Kim, Su-Yong Eun, Sung-Cherl Jung
Excessive influx and the subsequent rapid cytosolic elevation of Ca(2+) in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca(2+) level in normal as well as pathological conditions. Delayed rectifier K(+) channels (IDR channels) play a role to suppress membrane excitability by inducing K(+) outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca(2+)-mediated excitotoxic conditions...
March 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28278510/autocrine-vegf-and-il-8-promote-migration-via-src-vav2-rac1-pak1-signaling-in-human-umbilical-vein-endothelial-cells
#5
Li Ju, Zhiwen Zhou, Bo Jiang, Yue Lou, Xirong Guo
BACKGROUND/AIMS: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). METHODS: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs...
March 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28266558/selective-induction-of-alternatively-spliced-fynt-isoform-by-tnf-facilitates-persistent-inflammatory-responses-in-astrocytes
#6
Chingli Lee, Clara Y B Low, Siew Ying Wong, Mitchell K P Lai, Michelle G K Tan
Fyn tyrosine kinase has been implicated in the pathogenesis of Alzheimer's disease (AD). We have previously reported that upregulation of the FynT isoform in AD brains was partly associated with astrocyte activation. In this study, we demonstrated selective FynT induction in murine cortex and primary astrocyte culture after prolonged exposure to inflammatory stimulants, suggesting that FynT may mediate persistent neuroinflammation. To delineate the functional role of astrocytic FynT in association with TNF-mediated inflammatory responses, immortalized normal human astrocytes (iNHA) stably expressing FynT kinase constitutively active (FynT-CA) or kinase dead (FynT-KD) mutants were treated with TNF and compared for inflammatory responses using high-throughput real-time RT-PCR and Luminex multi-analyte immunoassays...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213973/transforming-growth-factor-%C3%AE-induces-bone-marrow-mesenchymal-stem-cell-migration-via-noncanonical-signals-and-n-cadherin
#7
Maria Jose Dubon, Jinyeong Yu, Sanghyuk Choi, Ki-Sook Park
Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28193869/perplexing-cooperative-folding-and-stability-of-a-low-sequence-complexity-polyproline-2-protein-lacking-a-hydrophobic-core
#8
Zachary P Gates, Michael C Baxa, Wookyung Yu, Joshua A Riback, Hui Li, Benoît Roux, Stephen B H Kent, Tobin R Sosnick
The burial of hydrophobic side chains in a protein core generally is thought to be the major ingredient for stable, cooperative folding. Here, we show that, for the snow flea antifreeze protein (sfAFP), stability and cooperativity can occur without a hydrophobic core, and without α-helices or β-sheets. sfAFP has low sequence complexity with 46% glycine and an interior filled only with backbone H-bonds between six polyproline 2 (PP2) helices. However, the protein folds in a kinetically two-state manner and is moderately stable at room temperature...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28178976/advanced-glycation-end-products-induce-brain-derived-neurotrophic-factor-release-from-human-platelets-through-the-src-family-kinase-activation
#9
Kazuo Furukawa, Ichiro Fuse, Yuriko Iwakura, Hidekazu Sotoyama, Osamu Hanyu, Hiroyuki Nawa, Hirohito Sone, Nobuyuki Takei
BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts beneficial effects not only on diabetic neuropathies but also on cardiovascular injury. There is argument regarding the levels of serum BDNF in patients with diabetes mellitus (DM). Because BDNF in peripheral blood is rich in platelets, this may represent dysregulation of BDNF release from platelets. Here we focused on advanced glycation end products (AGEs), which are elevated in patients with DM and have adverse effects on cardiovascular functions...
February 8, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28153500/endothelin-causes-transactivation-of-the-egfr-and-her2-in-non-small-cell-lung-cancer-cells
#10
Terry W Moody, Irene Ramos-Alvarez, Paula Moreno, Samuel A Mantey, Lisa Ridnour, David Wink, Robert T Jensen
Endothelin (ET)-1 is an important peptide in cancer progression stimulating cellular proliferation, tumor angiogenesis and metastasis. ET-1 binds with high affinity to the ETA receptor (R) and ETBR on cancer cells. High levels of tumor ET-1 and ETAR are associated with poor survival of lung cancer patients. Here the effects of ET-1 on epidermal growth factor (EGF)R and HER2 transactivation were investigated using non-small cell lung cancer (NSCLC) cells. ETAR mRNA was present in all 10 NSCLC cell lines examined...
January 31, 2017: Peptides
https://www.readbyqxmd.com/read/28122732/na-k-atpase-regulates-intercellular-communication-in-the-vascular-wall-via-csrc-kinase-dependent-connexin43-phosphorylation
#11
Lise Hangaard, Elena V Bouzinova, Christian Staehr, Vibeke S Dam, Sukhan Kim, Zijian Xie, Christian Aalkjaer, Vladimir V Matchkov
Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na,K-ATPase. The Na,K-ATPase is therefore important for synchronized VSMCs oscillatory activity, i.e. vasomotion. The signaling between the Na,K-ATPase and gap junctions is unknown. We tested here the hypothesis that that this signaling involves cSrc kinase. Intercellular communication was assessed by membrane capacitance measurements of electrically coupled VSMCs. Vasomotion in isometric myograph, input resistance and synchronized [Ca(2+)]i transients were used as readout for intercellular coupling in rat mesenteric small arteries in vitro...
January 25, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28108852/missing-the-target-the-neural-processing-underlying-the-omission-error
#12
Rinaldo Livio Perri, Donatella Spinelli, Francesco Di Russo
The omissions are infrequent errors consisting in missing responses to the target stimuli. This is the first study aimed at investigating the brain activities associated with omissions in a decision-making task. We recorded event-related potentials (ERPs) in 12 subjects which reported a suitable number of omissions in a visual go/no-go task. We investigated both the pre- and post-stimulus brain activities associated with correct and omitted trials. The electrical neuroimaging technique (BESA) was adopted to extract the anterior insula (aIns) activity associated with the prefrontal P2 component (pP2) peaking about 300 ms after the stimulus and reflecting the stimulus-response mapping process...
January 20, 2017: Brain Topography
https://www.readbyqxmd.com/read/28088327/cftr-impairment-upregulates-c-src-activity-through-il-1%C3%AE-autocrine-signaling
#13
María Macarena Massip-Copiz, Mariángeles Clauzure, Ángel Gabriel Valdivieso, Tomás Antonio Santa-Coloma
Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to 'CFTR-corrected' S9 cells...
January 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28072464/genistein-and-tyrphostin-ag556-decrease-ultra-rapidly-activating-delayed-rectifier-k-current-of-human-atria-by-inhibiting-egf-receptor-tyrosine-kinase
#14
Guo-Sheng Xiao, Yan-Hui Zhang, Wei Wu, Hai-Ying Sun, Yan Wang, Gui-Rong Li
BACKGROUND AND PURPOSE: The ultra-rapidly activating delayed rectifier K(+) current IKur (encoded by Kv 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). EXPERIMENTAL APPROACH: Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial IKur and hKv1...
March 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28072455/src-and-phospho-fak-kinases-are-activated-by-allopregnanolone-promoting-schwann-cells-motility-morphology-and-myelination
#15
Simona Melfi, Maria Magdalena Montt Guevara, Veronica Bonalume, Massimiliano Ruscica, Alessandra Colciago, Tommaso Simoncini, Valerio Magnaghi
Schwann cells' (SCs) development and maturation require coordinate and complementary interaction among several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs' fate, participating in regulation of SC adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SC motility and proliferation, which are crucial processes for nerve development, maturation and regeneration...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28049238/the-curves-exercise-suppresses-endotoxemia-in-korean-women-with-obesity
#16
Seon Ah Jin, Sun Kyeong Kim, Hee Jung Seo, Mijoo Kim, Kye Taek Ahn, Jun Hyung Kim, Jae Hyeong Park, Jae Hwan Lee, Si Wan Choi, Jin Ok Jeong
Obesity and metabolic syndrome is a worldwide pandemic and associated with high cardiovascular risk. Metabolic endotoxemia (ME) is thought to be an underlying molecular mechanism. It triggers toll-like receptor 4-mediated inflammatory adipokines and causes a chronic low grade inflammatory status, which results in cardiovascular risk increase. Exercise is the best nonpharmacological treatment to improve prognosis. In this study, we examined the circulating endotoxin level in Korean obese women and investigated effects of exercise on it...
February 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28044939/inhibition-of-tgf-%C3%AE-signaling-in-tumor-cells-by-small-molecule-src-family-kinase-inhibitors
#17
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnerta, Hendrik Ungefroren
In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated shown that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28011194/convergence-of-eicosanoid-and-integrin-biology-role-of-src-in-12-lox-activation
#18
Ashok-Kumar Dilly, Keqin Tang, Yande Guo, Sangeeta Joshi, Prasanna Ekambaram, Krishna Rao Maddipati, Yinlong Cai, Stephanie C Tucker, Kenneth V Honn
12-Lipoxygenase (12-LOX) metabolizes arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid, or 12(S)-HETE, a proinflammatory bioactive lipid implicated in tumor angiogenesis, growth, and metastasis. The mechanisms underlying 12-LOX-mediated signaling in cancer progression are still ill-defined. In the present study we demonstrate that 12-LOX phosphorylation and subsequent enzymatic activity occurs after integrin β4 stimulation and Src kinase recruitment to the integrin subunit. Inhibition of Src activity by PP2 or Src dominant-negative mutants reduced 12-LOX tyrosine phosphorylation and 12(S)-HETE production in response to integrin β4 stimulation in A431 cells...
February 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28003155/different-proactive-and-reactive-action-control-in-fencers-and-boxers-brain
#19
Valentina Bianco, Francesco Di Russo, Rinaldo Livio Perri, Marika Berchicci
Practicing sport at top level requires excellent physical and cognitive skills. The goal of the present study was to investigate whether specific sport practice may affect the preparation-perception-action stages of processing during a visuo-motor task requiring perceptual discrimination and fast response. We recruited 39 participants (two groups of professional fencers and boxers, and a control group; N=13 for each group) and measured behavioral performance and event-related potentials (ERPs) while performing a go/no-go task...
December 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27996167/intracellular-chloride-concentration-changes-modulate-il-1%C3%AE-expression-and-secretion-in-human-bronchial-epithelial-cultured-cells
#20
Mariángeles Clauzure, Ángel G Valdivieso, María M Massip-Copiz, Consuelo Mori, Andrea V Dugour, Juan M Figueroa, Tomás A Santa Coloma
Cystic fibrosis (CF) is caused by mutations in the CFTR gene, which encodes a cAMP-regulated chloride channel. Several cellular functions are altered in CF cells. However, it is not clear how the CFTR failure induces those alterations. We have found previously several genes differentially expressed in CF cells, including c-Src, MUC1, MTND4 and CISD1 (CFTR-dependent genes). Recently, we also reported the existence of several chloride-dependent genes, among them GLRX5 and RPS27. Here, varying the intracellular chloride concentration [Cl(-) ]i of IB3-1 CF bronchial epithelial cells, we show that IL-1β mRNA expression and secretion are also under Cl(-) modulation...
December 20, 2016: Journal of Cellular Biochemistry
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