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Gsk3 Inhibitor

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https://www.readbyqxmd.com/read/27909397/novel-non-phosphorylated-serine-9-21-gsk3%C3%AE-%C3%AE-antibodies-expanding-the-tools-for-studying-gsk3-regulation
#1
Tessa Grabinski, Nicholas M Kanaan
Glycogen synthase kinase 3 (GSK3) β and α are serine/threonine kinases involved in many biological processes. A primary mechanism of GSK3 activity regulation is phosphorylation of N-terminal serine (S) residues (S9 in GSK3β, S21 in GSK3α). Phosphorylation is inhibitory to GSK3 kinase activity because the phosphorylated N-terminus acts as a competitive inhibitor for primed substrates. Despite widespread interest in GSK3 across most fields of biology, the research community does not have reagents that specifically react with nonphosphoS9/21 GSK3β/α (the so-called "active" form)...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27907001/multifactorial-optimizations-for-directing-endothelial-fate-from-stem-cells
#2
Drew E Glaser, William S Turner, Nicole Madfis, Lian Wong, Jose Zamora, Nicholas White, Samuel Reyes, Andrew B Burns, Ajay Gopinathan, Kara E McCloskey
Embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells are attractive in vitro models of vascular development, therapeutic angiogenesis, and tissue engineering. However, distinct ESC and iPS cell lines respond differentially to the same microenvironmental factors. Developing improved/optimized differentiation methodologies tailored/applicable in a number of distinct iPS and ESC lines remains a challenge in the field. Currently published methods for deriving endothelial cells (EC) robustly generate high numbers of endothlelial progenitor cells (EPC) within a week, but their maturation to definitive EC is much more difficult, taking up to 2 months and requiring additional purification...
2016: PloS One
https://www.readbyqxmd.com/read/27880024/insect-cold-hardiness-the-role-of-mitogen-activated-protein-kinase-and-akt-signalling-in-freeze-avoiding-larvae-of-the-goldenrod-gall-moth-epiblema-scudderiana
#3
J Zhang, K B Storey
Larvae of the goldenrod gall moth, Epiblema scudderiana, use the freeze avoidance strategy of cold hardiness to survive the winter. Here we report that protein kinase-dependent signal transduction featuring mitogen-activated protein kinase (MAPK) signalling cascades (extracellular signal regulated kinase, c-jun N-terminal kinase and p38 MAPK pathways) and the Akt (also known as protein kinase B, or PKB) pathway could be integral parts of the development of cold hardiness by E. scudderiana. We used Luminex technology to assess the protein levels and phosphorylation status of key components and downstream targets of those pathways in larvae in response to low temperature acclimation...
November 23, 2016: Insect Molecular Biology
https://www.readbyqxmd.com/read/27863047/theoretical-studies-on-the-selective-mechanisms-of-gsk3%C3%AE-and-cdk2-by-molecular-dynamics-simulations-and-free-energy-calculations
#4
Sufang Zhao, Jingyu Zhu, Lei Xu, Jian Jin
Glycogen synthase kinase 3 (GSK3) is a serine/threonine protein kinase which is widely involved in cell signaling and controls a broad number of cellular functions. GSK3 contains α and β isoforms, and GSK3β has received more attention and becomes an attractive drug target for the treatment of several diseases. The binding pocket of Cyclin-dependent kinases 2 (CDK2) shares high sequence identity to that of GSK3β, and therefore the design of highly selective inhibitors towards GSK3β remains a big challenge...
November 11, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27849005/insulin-igf-signaling-affects-cell-transformation-in-the-balb-c-3t3-cell-model
#5
Doerte Poburski, Christiane Leovsky, Josefine Barbara Boerner, Luisa Szimmtenings, Michael Ristow, Michael Glei, René Thierbach
The increased cancer mortality of diabetes type 2 patients is most likely an evidence of the tight connection between tumor development and energy metabolism. A major focus of today's research is still the identification of key proteins of both diseases and the development of corresponding inhibitors. In this study we combined the two-stage BALB/c-3T3 cell transformation assay (BALB-CTA) with the IR/IGF-1R inhibitor OSI-906 (linsitinib) and analyzed alterations in protein activity and energy parameters in non-transformed as well as transformed cells...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27826801/erratum-to-glycogen-synthase-kinase-3-gsk3-inhibitor-sb216763-promotes-the-conversion-of-human-umbilical-cord-mesenchymal-stem-cells-into-neural-precursors-in-adherent-culture
#6
Liyang Gao, Mingyan Zhao, Peng Li, Junchao Kong, Zhijun Liu, Yonghua Chen, Rui Huang, Jiaqi Chu, Juanhua Quan, Rong Zeng
No abstract text is available yet for this article.
November 8, 2016: Human Cell
https://www.readbyqxmd.com/read/27752079/dixdc1-contributes-to-psychiatric-susceptibility-by-regulating-dendritic-spine-and-glutamatergic-synapse-density-via-gsk3-and-wnt-%C3%AE-catenin-signaling
#7
P-M Martin, R E Stanley, A P Ross, A E Freitas, C E Moyer, A C Brumback, J Iafrati, K S Stapornwongkul, S Dominguez, S Kivimäe, K A Mulligan, M Pirooznia, W R McCombie, J B Potash, P P Zandi, S M Purcell, S J Sanders, Y Zuo, V S Sohal, B N R Cheyette
Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls...
October 18, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27723376/ketamine-up-regulates-a-cluster-of-intronic-mirnas-within-the-serotonin-receptor-2c-gene-by-inhibiting-glycogen-synthase-kinase-3
#8
Steven F Grieco, Dmitry Velmeshev, Marco Magistri, Hagit Eldar-Finkelman, Mohammad A Faghihi, Richard S Jope, Eleonore Beurel
OBJECTIVES: We examined mechanisms that contribute to the rapid antidepressant effect of ketamine in mice that is dependent on glycogen synthase kinase-3 (GSK3) inhibition. METHODS: We measured serotonergic (5HT)-2C-receptor (5HTR2C) cluster microRNA (miRNA) levels in mouse hippocampus after administering an antidepressant dose of ketamine (10 mg/kg) in wild-type and GSK3 knockin mice, after GSK3 inhibition with L803-mts, and in learned helpless mice. RESULTS: Ketamine up-regulated cluster miRNAs 448-3p, 764-5p, 1264-3p, 1298-5p and 1912-3p (2- to 11-fold)...
October 10, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27688851/anti-malarial-activities-of-two-soil-actinomycete-isolates-from-sabah-via-inhibition-of-glycogen-synthase-kinase-3%C3%AE
#9
Dhiana Efani Dahari, Raifana Mohamad Salleh, Fauze Mahmud, Lee Ping Chin, Noor Embi, Hasidah Mohd Sidek
Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection...
August 2016: Tropical Life Sciences Research
https://www.readbyqxmd.com/read/27677634/selective-and-effective-targeting-of-chronic-myeloid-leukemia-stem-cells-by-topoisomerase-ii-inhibitor-etoposide-in-combination-with-imatinib-mesylate-in-vitro
#10
Man-Yu Liu, Wei-Zhang Wang, Fen-Fang Liao, Qing-Qing Wu, Xiang-Hua Lin, Yong-Hen Chen, Lin Cheng, Xiao-Bao Jin, Jia-Yong Zhu
Imatinib mesylate (IM) and other BCR-ABL tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) patient survival markedly but fail to eradicate quiescent CML leukemia stem cells (LSCs). Thus, strategies targeting LSCs are required to induce long-term remission and achieve cure. Here, we investigated the ability of topoisomerase II (Top II) inhibitor etoposide (Eto) to target CML LSCs. Treatment with Eto combined with IM markedly induced apoptosis in primitive CML CD34(+) CD38(-) stem cells resistant to eradication by IM alone, but not in normal hematopoietic stem cells, CML and normal mature CD34(-) cells, and other leukemia and lymphoma cell lines...
September 28, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27633818/inhibition-of-the-integrin-signal-constitutes-a-mouse-ips-cell-niche
#11
Sayaka Higuchi, Sawako Yoshina, Shohei Mitani
Stem cells are regulated by their surrounding microenvironments, called niche, such as cell-cell interaction and extracellular matrix. Classically, feeder cells as a niche have been used in the culture of iPS cells from both the mouse and the human. However, the regulation mechanism of stem cells by feeder cells as a niche still have been partially unclear. In this study, we used three murine iPS cell lines, iPS-MEF-Ng-20D-17, iPS-MEF-Ng-178B-5 and iPS-MEF-Fb/Ng-440A-3, which were generated by different reprogramming methods...
September 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27630757/gsk3-signalling-and-redox-status-in-bipolar-disorder-evidence-from-lithium-efficacy
#12
REVIEW
Antonina Luca, Carmela Calandra, Maria Luca
Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27604750/glycogen-synthase-kinase-3-gsk3-inhibitor-sb216763-promotes-the-conversion-of-human-umbilical-cord-mesenchymal-stem-cells-into-neural-precursors-in-adherent-culture
#13
Liyang Gao, Mingyan Zhao, Peng Li, Junchao Kong, Zhijun Liu, Yonghua Chen, Rui Huang, Jiaqi Chu, Juanhua Quan, Rong Zeng
The ability to generate neural progenitor cells from human umbilical cord mesenchymal stem cells (hUC-MSCs) has provided an option to treat neurodegenerative diseases. To establish a method for this purpose, we characterized the early neural markers of hUC-MSCs-derived cells under different conditions. We found that neither the elimination of signals for alternative fate nor N2 supplement was sufficient to differentiate hUC-MSCs into neural precursor cells, but the GSK3 inhibitor SB216763 could promote an efficient neural commitment of hUC-MSCs...
September 7, 2016: Human Cell
https://www.readbyqxmd.com/read/27588407/defective-cftr-%C3%AE-catenin-interaction-promotes-nf-%C3%AE%C2%BAb-nuclear-translocation-and-intestinal-inflammation-in-cystic-fibrosis
#14
Kaisheng Liu, Xiaohu Zhang, Jie Ting Zhang, Lai Ling Tsang, Xiaohua Jiang, Hsiao Chang Chan
While inflammation with aberrant activation of NF-κB pathway is a hallmark of cystic fibrosis (CF), the molecular mechanisms underlying the link between CFTR defect and activation of NF-κB-mediated pro-inflammatory response remain elusive. Here, we investigated the link between CFTR defect and NF-κB activation in ΔF508cftr-/- mouse intestine and human intestinal epithelial cell lines. Our results show that the NF-κB/COX-2/PGE2 pathway is activated whereas the β-catenin pathway is suppressed in CF mouse intestine and CFTR-knockdown cells...
August 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27582689/acute-ethanol-inhibition-of-%C3%AE-oscillations-is-mediated-by-akt-and-gsk3%C3%AE
#15
JianGang Wang, JingXi Zhao, ZhiHua Liu, FangLi Guo, Yali Wang, Xiaofang Wang, RuiLing Zhang, Martin Vreugdenhil, Chengbiao Lu
Hippocampal network oscillations at gamma band frequency (γ, 30-80 Hz) are closely associated with higher brain functions such as learning and memory. Acute ethanol exposure at intoxicating concentrations (≥50 mM) impairs cognitive function. This study aimed to determine the effects and the mechanisms of acute ethanol exposure on γ oscillations in an in vitro model. Ethanol (25-100 mM) suppressed kainate-induced γ oscillations in CA3 area of the rat hippocampal slices, in a concentration-dependent, reversible manner...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27580988/luteolin-inhibits-proliferation-and-induces-apoptosis-of-human-placental-choriocarcinoma-cells-by-blocking-the-pi3k-akt-pathway-and-regulating-sterol-regulatory-element-binding-protein-activity
#16
Whasun Lim, Changwon Yang, Fuller W Bazer, Gwonhwa Song
Luteolin is a natural compound known for its anticancer effects on various human cancers by regulating signal transduction cascades. However, the effects of luteolin on human placental choriocarcinoma are not known. Results of the present study revealed that luteolin decreased viability of JAR and JEG-3 cells, which are valuable placental models, in a dose-dependent manner, and it induced apoptosis and loss of mitochondrial membrane potential in JAR and JEG-3 cells. The results also suggested that the PI3K/AKT pathway was inhibited by luteolin treatment of JAR and JEG-3 cells in a dose- and time-dependent manner...
October 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27580020/mulberry-anthocyanin-extract-ameliorates-insulin-resistance-by-regulating-pi3k-akt-pathway-in-hepg2-cells-and-db-db-mice
#17
Fujie Yan, Guanhai Dai, Xiaodong Zheng
This study evaluated the capacity of mulberry anthocyanin extract (MAE) on insulin resistance amelioration in HepG2 cells induced by high glucose and palmitic acid and diabetes-related metabolic changes in type 2 diabetic mice. In vitro, MAE alleviated insulin resistance in HepG2 cells and increased glucose consumption, glucose uptake and glycogen content. Enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were decreased due to PPARγ coactivator 1α (PGC-1α) and forkhead box protein O1 (FOXO1) inhibition...
October 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27576342/interplay-between-intergrin-linked-kinase-and-ribonuclease-inhibitor-affects-growth-and-metastasis-of-bladder-cancer-through-signaling-ilk-pathways
#18
Xiang Zhuang, Mengxin Lv, Zhenyu Zhong, Luyu Zhang, Rong Jiang, Junxia Chen
BACKGROUND: Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial-mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27574112/glycogen-synthase-kinase-3-is-involved-in-glycogen-metabolism-control-and-embryogenesis-of-rhodnius-prolixus
#19
Flávia B Mury, Magda D Lugon, Rodrigo Nunes DA Fonseca, Jose R Silva, Mateus Berni, Helena M Araujo, Marcio Ribeiro Fontenele, Leonardo Araujo DE Abreu, Marílvia Dansa, Glória Braz, Hatisaburo Masuda, Carlos Logullo
Rhodnius prolixus is a blood-feeding insect that transmits Trypanosoma cruzi and Trypanosoma rangeli to vertebrate hosts. Rhodnius prolixus is also a classical model in insect physiology, and the recent availability of R. prolixus genome has opened new avenues on triatomine research. Glycogen synthase kinase 3 (GSK-3) is classically described as a key enzyme involved in glycogen metabolism, also acting as a downstream component of the Wnt pathway during embryogenesis. GSK-3 has been shown to be highly conserved among several organisms, mainly in the catalytic domain region...
October 2016: Parasitology
https://www.readbyqxmd.com/read/27565262/locostatin-a-disrupter-of-raf-kinase-inhibitor-protein-inhibits-extracellular-matrix-production-proliferation-and-migration-in-human-uterine-leiomyoma-and-myometrial-cells
#20
Milijana Janjusevic, Stefania Greco, Soriful Islam, Clara Castellucci, Andrea Ciavattini, Paolo Toti, Felice Petraglia, Pasquapina Ciarmela
OBJECTIVE: To investigate the presence of Raf kinase inhibitor protein (RKIP) in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation, and migration in human myometrial and leiomyoma cells. DESIGN: Laboratory study. SETTING: Human myometrium and leiomyoma. PATIENT(S): Thirty premenopausal women who were admitted to the hospital for myomectomy or hysterectomy...
August 23, 2016: Fertility and Sterility
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