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https://www.readbyqxmd.com/read/28935982/glycogen-synthase-kinase-3%C3%AE-inhibition-links-mitochondrial-dysfunction-extracellular-matrix-remodelling-and-terminal-differentiation-in-chondrocytes
#1
S Guidotti, M Minguzzi, D Platano, S Santi, G Trisolino, G Filardo, E Mariani, R M Borzì
Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935820/lack-of-serum-and-glucocorticoid-inducible-kinase-3-leads-to-podocyte-dysfunction
#2
Li-Qin Peng, Hong Zhao, Song Liu, Ya-Pei Yuan, Cheng-Yan Yuan, Mercy-Julian Mwamunyi, David Pearce, Li-Jun Yao
Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28930226/shenlinglan-influences-the-attachment-and-migration-of-ovarian-cancer-cells-potentially-through-the-gsk3-pathway
#3
Sioned Owen, Fiona Ruge, Yunong Gao, Ying Yang, Jianqing Hou, Jian Chen, Yi Feng, Huiming Zhang, Yong Gao, Hongtao Wang, Cong Wei, Yiling Wu, Wen G Jiang
Background: Ovarian cancer presents a major clinical challenge in the UK. Glycogen synthase kinase-3 (GSK-3) has been linked to cancer. This study tested the impact of ShenLingLan (SLDM) on ovarian cancer cell behaviour and its links to GSK-3. Methods: Fresh ovarian tumours (n = 52) were collected and processed. Histopathologcial and clinical information were collected and analysed against GSK-3 transcript levels using quantitative PCR (qPCR). Immortalised ovarian cancer cells' protein alterations in response to SLDM were identified using a Kinexus™ protein kinase array...
February 21, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28926938/integrin-activation-contributes-to-lower-cisplatin-sensitivity-in-mv3-melanoma-cells-by-inducing-the-wnt-signalling-pathway
#4
Maria B R Piva, Bastian Jakubzig, Gerd Bendas
BACKGROUND: integrins have been associated with the development of chemotherapy resistant tumour cells, mostly those of hematopoietic origin, by mediating the binding to the extracellular matrix. The relevance for solid tumour cells and the underlying mechanisms remain elusive. METHODS: using MTT assays, we detected the loss in cisplatin sensitivity of human MV3 melanoma cells upon integrin activation. Underlying cellular pathways were evaluated by flow cytometry...
September 16, 2017: Cancers
https://www.readbyqxmd.com/read/28925399/dock4-promotes-loss-of-proliferation-in-glioblastoma-progenitor-cells-through-nuclear-beta-catenin-accumulation-and-subsequent-mir-302-367-cluster-expression
#5
D N Debruyne, L Turchi, F Burel-Vandenbos, M Fareh, F Almairac, V Virolle, D Figarella-Branger, N Baeza-Kallee, P Lagadec, V Kubiniek, P Paquis, D Fontaine, M-P Junier, H Chneiweiss, T Virolle
Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28916722/phosphoproteomics-reveals-that-glycogen-synthase-kinase-3-phosphorylates-multiple-splicing-factors-and-is-associated-with-alternative-splicing
#6
Mansi Y Shinde, Simone Sidoli, Katarzyna Kulej, Michael J Mallory, Caleb M Radens, Amanda Reicherter, Rebecca L Myers, Yoseph Barash, Kristen W Lynch, Benjamin A Garcia, Peter S Klein
Glycogen Synthase Kinase-3 (GSK-3) is a constitutively active, ubiquitously expressed protein kinase that regulates multiple signaling pathways. In vitro kinase assays and genetic and pharmacological manipulations of GSK-3 have identified more than 100 putative GSK-3 substrates in diverse cell types. Many more have been predicted on the basis of a recurrent GSK-3 consensus motif (pS/pTXXXS/T), but this prediction has not been tested by analyzing the GSK-3 phosphoproteome. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry (MS) techniques to analyze the repertoire of GSK-3-dependent phosphorylation in mouse embryonic stem cells (ESCs), we found that ~2...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28887744/microrna-203-suppresses-proliferation-in-liver-cancer-associated-with-pik3ca-p38-mapk-c-jun-and-gsk3-signaling
#7
Annie Zhang, Jaganathan Lakshmanan, Amirreza Motameni, Brian G Harbrecht
Primary liver cancer (hepatocellular carcinoma, HCC) is a leading cause of cancer-related deaths, and alternative ways to treat this disease are urgently needed. In recent years, novel approaches to cancer treatment have been based on microRNAs, small non-coding RNA molecules that play a crucial role in cancer progression by regulating gene expression. Overexpression of some microRNAs has shown therapeutic potential, but whether or not this was the case for microRNA-203 (miR-203) in liver cancer was unknown...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28887016/myotome-adaptability-confers-developmental-robustness-to-somitic-myogenesis-in-response-to-fibre-number-alteration
#8
Shukolpa D Roy, Victoria C Williams, Tapan G Pipalia, Kuoyu Li, Christina L Hammond, Stefanie Knappe, Robert D Knight, Simon M Hughes
Balancing the number of stem cells and their progeny is crucial for tissue development and repair. Here we examine how cell numbers and overall muscle size are tightly regulated during zebrafish somitic muscle development. Muscle stem/precursor cell (MPCs) expressing Pax7 are initially located in the dermomyotome (DM) external cell layer, adopt a highly stereotypical distribution and thereafter a proportion of MPCs migrate into the myotome. Regional variations in the proliferation and terminal differentiation of MPCs contribute to growth of the myotome...
September 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28883123/post-translational-modification-of-the-interferon-gamma-receptor-alters-its-stability-and-signaling
#9
James D Londino, Dexter L Gullick, Travis B Lear, Tomeka L Suber, Nathaniel M Weathington, Luke S Masa, Bill B Chen, Rama K Mallampalli
The IFN gamma receptor 1 (IFNGR1) binds IFN gamma and activates gene transcription pathways crucial for controlling bacterial and viral infections. Although decreases in IFNGR1 surface levels have been demonstrated to inhibit IFN gamma signaling, little is known regarding the molecular mechanisms controlling receptor stability. Here we show in epithelial and monocytic cell lines that IFNGR1 displays K48 polyubiquitination, is proteasomally degraded, and harbors three ubiquitin acceptor sites at K277, K279, and K285...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28829772/correction-ovate-family-protein-8-positively-mediates-brassinosteroid-signaling-through-interacting-with-the-gsk3-like-kinase-in-rice
#10
Chao Yang, Wenjin Shen, Yong He, Zhihong Tian, Jianxiong Li
[This corrects the article DOI: 10.1371/journal.pgen.1006118.].
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#11
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28817575/mck1-is-a-novel-regulator-of-myo-inositol-phosphate-synthase-mips-that-is-required-for-inhibition-of-inositol-synthesis-by-the-mood-stabilizer-valproate
#12
Wenxi Yu, Joshua Daniel, Dhara Mehta, Krishna Rao Maddipati, Miriam L Greenberg
Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS), which catalyzes the rate-limiting step of inositol synthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28817124/directed-differentiation-and-long-term-maintenance-of-epicardial-cells-derived-from-human-pluripotent-stem-cells-under-fully-defined-conditions
#13
Xiaoping Bao, Xiaojun Lian, Tongcheng Qian, Vijesh J Bhute, Tianxiao Han, Sean P Palecek
Here, we describe how to efficiently direct human pluripotent stem cells (hPSCs) differentiation into self-renewing epicardial cells in a completely defined, xeno-free system by temporal modulation of regulators of canonical Wnt signaling. Appropriate differentiation-stage-specific application of Gsk3 inhibitor, Wnt inhibitor, and Gsk3 inhibitor (GiWiGi) is sufficient to produce cells expressing epicardial markers and exhibiting epicardial phenotypes with a high yield and purity from multiple hPSC lines in 16 d...
September 2017: Nature Protocols
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#14
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28803855/elucidating-the-functions-of-brain-gsk3%C3%AE-possible-synergy-with-gsk3%C3%AE-upregulation-and-reversal-by-antidepressant-treatment-in-a-mouse-model-of-depressive-like-behaviour
#15
Dmitrii Pavlov, Nataliia Markova, Lucien Bettendorff, Vladimir Chekhonin, Igor Pomytkin, Viktoria Lioudyno, Andrei Svistunov, Eugene Ponomarev, Klaus-Peter Lesch, Tatyana Strekalova
Glycogen synthase kinase 3 (GSK3) has been linked to the mechanisms of stress, mood regulation, and the effects of antidepressants. The functions of the GSK3β isoform have been extensively investigated, but little is known about the α-isoform, although they may functionally related. In a recently established modified swim test with a third delayed swim exposure, brain GSK3β mRNA expression positively correlated with floating behaviour on the third test. A two-week-long pretreatment regime with imipramine (7...
August 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28800359/the-selective-pi3k%C3%AE-inhibitor-byl719-as-a-novel-therapeutic-option-for-neuroendocrine-tumors-results-from-multiple-cell-line-models
#16
Svenja Nölting, Jakob Rentsch, Helma Freitag, Katharina Detjen, Franziska Briest, Markus Möbs, Victoria Weissmann, Britta Siegmund, Christoph J Auernhammer, Elke Tatjana Aristizabal Prada, Michael Lauseker, Ashley Grossman, Samantha Exner, Christian Fischer, Carsten Grötzinger, Jörg Schrader, Patricia Grabowski
BACKGROUND/AIMS: The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS: Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28795276/topiramate-via-nmda-ampa-kainate-gabaa-and-alpha2-receptors-and-by-modulation-of-creb-bdnf-and-akt-gsk3-signaling-pathway-exerts-neuroprotective-effects-against-methylphenidate-induced-neurotoxicity-in-rats
#17
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Tabassom Beiranvand, Shiva Mozaffari
Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist...
August 9, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28790065/gsk-3-inhibition-drives-maturation-of-nk-cells-and-enhances-their-antitumor-activity
#18
Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey K Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart E Abbot, Daniel Shoemaker, Yenan T Bryceson, Bruce R Blazar, Scott Wolchko, Sarah Cooley, Jeffrey S Miller
Maturation of human natural killer cells (NK cells) as defined by accumulation of cell surface expression of CD57 is associated with increased cytotoxic character and TNF and IFN-γ production upon target cell recognition. Notably, multiple studies point to a unique role for CD57(+) NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacological inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL-15 greatly enhances CD57 upregulation and late-stage maturation...
August 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28780599/liraglutide-ameliorates-cardiotoxicity-induced-by-doxorubicin-in-rats-through-the-akt-gsk-3%C3%AE-signaling-pathway
#19
Noha A T Abbas, Soad L Kabil
Doxorubicin (Dox)-induced cardiotoxicity constitutes the major adverse effect that limited its use. We investigated the possible protective effects of liraglutide on Dox-induced cardiotoxicity in rats. Rats were divided into the following groups: control group rats received normal saline [1 ml/kg, intraperitoneal (i.p.)]; doxorubicin group rats received doxorubicin (1.25 mg/kg, i.p.), four times per week for 4 weeks; and liraglutide group rats received doxorubicin (1.25 mg/kg, i.p.) four times per week for 4 weeks then received liraglutide (100 μg/kg, i...
August 5, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28772167/glycogen-synthase-kinase-3-inhibition-sensitizes-human-induced-pluripotent-stem-cells-to-thiol-containing-antioxidants-induced-apoptosis
#20
Chengyi Tu, Robert Xu, Meghana Koleti, Janet Zoldan
Inhibition of glycogen synthase kinase 3 (GSK3) is an extensively used strategy to activate Wnt pathway for pluripotent stem cell (PSC) differentiation. However, the effects of such inhibition on PSCs, besides upregulating the Wnt pathway, have rarely been investigated despite that GSK3 is broadly involved in other cellular activities such as insulin signaling and cell growth/survival regulation. Here we describe a previously unknown synergistic effect between GSK3 inhibition (e.g., Chir99021 and LY2090314) and various normally non-toxic thiol-containing antioxidants (e...
August 2017: Stem Cell Research
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