keyword
MENU ▼
Read by QxMD icon Read
search

Gsk3 Inhibitor

keyword
https://www.readbyqxmd.com/read/29328365/nuclear-gsk3%C3%AE-induces-dna-double-strand-break-repair-by-phosphorylating-53bp1-in-glioblastoma
#1
Yong Yang, Tiantian Lei, Suya Du, Rongsheng Tong, Hailian Wang, Jiao Yang, Juan Huang, Minghan Sun, Yi Wang, Zhi Dong
Glioblastoma is the most malignant and lethal subtype brain tumors with high risk of recurrence and therapeutic resistance. Emerging evidence has indicated that glycogen synthesis kinase 3 (GSK3)β plays oncogenic roles in multiple tumor types; however, the underlying mechanisms remain largely unknown. It has also been demonstrated that p53 binding protein 1 (53BP1) plays a central role in DNA double-strand break (DSB) repair. This study aimed to reveal the significance of GSK3β translocation from the cytoplasm to the nucleus, and to determine whether GSK3β induces DNA DSB repair in the nuclei of glioblastoma cells via phospho-53BP1...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29316313/microrna-21-promotes-glioma-cell-proliferation-and-inhibits-senescence-and-apoptosis-by-targeting-spry1-via-the-pten-pi3k-akt-signaling-pathway
#2
Chang Chai, Lai-Jun Song, Shuang-Yin Han, Xi-Qing Li, Ming Li
AIMS: Our study aims to investigate the effect of microRNA-21 (miR-21) on the proliferation, senescence, and apoptosis of glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway. METHODS: Glioma tissues and brain tissues were collected for this study after surgical decompression for traumatic brain injury. RT-qPCR was employed to measure mRNA levels of miR-21, SPRY1, PTEN, PI3K, and AKT, and Western blotting was conducted to determine protein levels of SPRY1, PTEN, PI3K, AKT, p-AKT, Caspase-3, Caspase-9, P53, GSK3, and p-GSK3...
January 5, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29298515/vitex-rotundifolia-fruit-suppresses-the-proliferation-of-human-colorectal-cancer-cells-through-down-regulation-of-cyclin-d1-and-cdk4-via-proteasomal-dependent-degradation-and-transcriptional-inhibition
#3
Hun Min Song, Gwang Hun Park, Su Bin Park, Hyun-Seok Kim, Ho-Jun Son, Yurry Um, Jin Boo Jeong
Viticis Fructus (VF) as the dried fruit from Vitex rotundifolia L. used as a traditional medicine for treating inflammation, headache, migraine, chronic bronchitis, eye pain, and gastrointestinal infections has been reported to have antiproliferative effects against various cancer cells, including breast, lung and colorectal cancer cells. However, the molecular mechanisms by which VF mediates the inhibitory effect of the proliferation of cancer cells have not been elucidated in detail. In this study, we investigated the molecular mechanism of VF on the down-regulation of cyclin D1 and CDK4 level associated with cancer cell proliferation...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29247183/rab-gtpase-binding-effector-protein-2-rabep2-is-a-primed-substrate-for-glycogen-synthase-kinase-3-gsk3
#4
Lisa Logie, Lidy Van Aalten, Axel Knebel, Thomas Force, C James Hastie, Hilary MacLauchlan, David G Campbell, Robert Gourlay, Alan Prescott, Jane Davidson, Will Fuller, Calum Sutherland
Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29244860/lithium-reduces-blood-glucose-levels-but-aggravates-albuminuria-in-btbr-ob-ob-mice
#5
Theun de Groot, Lars Damen, Leanne Kosse, Mohammad Alsady, Rosalinda Doty, Ruben Baumgarten, Susan Sheehan, Johan van der Vlag, Ron Korstanje, Peter M T Deen
Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy...
2017: PloS One
https://www.readbyqxmd.com/read/29218084/regulation-of-osteogenic-differentiation-by-dna-methylation-of-the-dishevelled-gene-in-bone-marrow-mesenchymal-stem-cells
#6
Xiaofeng Han, Xinfeng Li, Guibin Zhong, Zude Liu
Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional differentiation potential, which can be used as seed cells to repair and reconstruct many types of tissues and organs following injury or disease. Osteogenic differentiation involves a variety of pathway and factors, including cytokines, growth factors, and hormones. In the present study, we investigated the potential role of Dishevelled in osteogenic differentiation of BMSCs in induction medium containing the methyltransferase inhibitor 5-aza-2'-deoxycytidine...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29212798/the-gsk3-kinase-inhibitor-lithium-produces-unexpected-hyperphosphorylation-of-%C3%AE-catenin-a-gsk3-substrate-in-human-glioblastoma-cells
#7
Ata Ur Rahman Mohammed Abdul, Bhagya De Silva, Ronald K Gary
Lithium salt is a classic glycogen synthase kinase 3 (GSK3) inhibitor. Beryllium is a structurally-related inhibitor that is more potent but relatively uncharacterized. This study examined the effects of these inhibitors on the phosphorylation of endogenous GSK3 substrates. In NIH-3T3 cells, both salts caused a decrease in phosphorylated glycogen synthase, as expected. GSK3 inhibitors produce enhanced phosphorylation of Ser9 of GSK3β via a positive feedback mechanism, and both salts elicited this enhancement...
December 6, 2017: Biology Open
https://www.readbyqxmd.com/read/29207259/a-chemical-genetic-approach-reveals-the-distinct-roles-of-gsk3%C3%AE-and-gsk3%C3%AE-in-regulating-embryonic-stem-cell-fate
#8
Xi Chen, Ruizhe Wang, Xu Liu, Yongming Wu, Tao Zhou, Yujia Yang, Andrew Perez, Ying-Chu Chen, Liang Hu, Jean Paul Chadarevian, Amir Assadieskandar, Chao Zhang, Qi-Long Ying
Glycogen synthase kinase 3 (GSK3) plays a central role in diverse cellular processes. GSK3 has two mammalian isozymes, GSK3α and GSK3β, whose functions remain ill-defined because of a lack of inhibitors that can distinguish between the two highly homologous isozymes. Here, we show that GSK3α and GSK3β can be selectively inhibited in mouse embryonic stem cells (ESCs) using a chemical-genetic approach. Selective inhibition of GSK3β is sufficient to maintain mouse ESC self-renewal, whereas GSK3α inhibition promotes mouse ESC differentiation toward neural lineages...
December 4, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29203592/correction-of-gsk3%C3%AE-at-young-age-prevents-muscle-pathology-in-mice-with-myotonic-dystrophy-type-1
#9
Christina Wei, Lauren Stock, Leila Valanejad, Zachary A Zalewski, Rebekah Karns, Jack Puymirat, David Nelson, David Witte, Jim Woodgett, Nikolai A Timchenko, Lubov Timchenko
Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats (HSALR ) model]...
December 4, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29180818/oct4-supports-extended-lif-independent-self-renewal-and-maintenance-of-transcriptional-and-epigenetic-networks-in-embryonic-stem-cells
#10
Runsheng He, Besa Xhabija, Batool Al-Qanber, Benjamin L Kidder
Embryonic stem (ES) cell pluripotency is governed by OCT4-centric transcriptional networks. Conventional ES cells can be derived and maintained in vitro with media containing the cytokine leukemia inhibitory factor (LIF), which propagates the pluripotent state by activating STAT3 signaling, and simultaneous inhibition of glycogen synthase kinase-3 (GSK3) and MAP kinase/ERK kinase signaling. However, it is unclear whether overexpression of OCT4 is sufficient to overcome LIF-dependence. Here, we show that inducible expression of OCT4 (iOCT4) supports long-term LIF-independent self-renewal of ES cells cultured in media containing fetal bovine serum (FBS) and a glycogen synthase kinase-3 (GSK3) inhibitor, and in serum-free media...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29161257/regulation-of-camp-and-gsk3-signaling-pathways-contributes-to-the-neuronal-conversion-of-glioma
#11
Jinsoo Oh, Yongbo Kim, Lihua Che, Jeong Beom Kim, Gyeong Eon Chang, Eunji Cheong, Seok-Gu Kang, Yoon Ha
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator)...
2017: PloS One
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#12
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29092089/notch-wnt-cross-signalling-regulates-stemness-of-dental-pulp-stem-cells-through-expression-of-neural-crest-and-core-pluripotency-factors
#13
V Uribe-Etxebarria, J Luzuriaga, P García-Gallastegui, A Agliano, F Unda, G Ibarretxe
Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal...
November 1, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/29024409/the-natural-agent-rhein-induces-%C3%AE-catenin-degradation-and-tumour-growth-arrest
#14
Shu Liu, Jiao Wang, Ting Shao, Peiying Song, Qingbin Kong, Hui Hua, Ting Luo, Yangfu Jiang
The natural agent rhein is an ananthraquinone derivative of rhubarb, which has anticancer effects. To determine the mechanisms underlying the anticancer effects of rhein, we detected the effect of rhein on several oncoproteins. Here, we show that rhein induces β-catenin degradation in both hepatoma cell HepG2 and cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens the half-life of β-catenin. The proteasome inhibitor MG132 blunts the downregulation of β-catenin by rhein. The induction of β-catenin degradation by rhein is dependent on GSK3 but independent of Akt...
October 11, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29021340/downregulation-of-the-wnt-%C3%AE-catenin-signaling-pathway-by-cacnb4
#15
Mohamad Rima, Marwa Daghsni, Anaïs Lopez, Ziad Fajloun, Lydie Lefrancois, Mireia Dunach, Yasuo Mori, Philippe Merle, Juan L Brusés, Michel de Waard, Michel Ronjat
The β4 isoform of the β-subunits of Voltage-Gated Calcium Channel regulates cell proliferation and cell cycle progression. Herein we show that co-expression of the β4-subunit with actors of the canonical Wnt/β-catenin signaling pathway in a hepatoma cell line inhibits Wnt responsive gene transcription and decreases cell division, in agreement with the role of the Wnt pathway in cell proliferation. β4-subunit-mediated inhibition of Wnt signaling is observed in the presence of LiCl, an inhibitor of GSK3 that promotes β-catenin translocation to the nucleus...
October 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29016121/synthesis-binding-mode-and-antihyperglycemic-activity-of-potent-and-selective-5-imidazol-2-yl-4-phenylpyrimidin-2-yl-2-2-pyridylamino-ethyl-amine-inhibitors-of-glycogen-synthase-kinase-3
#16
Allan S Wagman, Rustum S Boyce, Sean P Brown, Eric Fang, Dane Goff, Johanna M Jansen, Vincent P Le, Barry H Levine, Simon C Ng, Zhi-Jie Ni, John M Nuss, Keith B Pfister, Savithri Ramurthy, Paul A Renhowe, David B Ring, Wei Shu, Sharadha Subramanian, Xiaohui A Zhou, Cynthia M Shafer, Stephen D Harrison, Kirk W Johnson, Dirksen E Bussiere
In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We developed efficient synthetic routes to explore a wide variety of substitution patterns and convergently access a diverse array of analogues. Compound 1 (CHIR-911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the C-5 position, phenyl groups at C-4, and a variety of differently substituted linker and aminopyridine moieties attached at the C-2 position...
October 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28993455/ehrlichia-activation-of-wnt-pi3k-mtor-signaling-inhibits-autolysosome-generation-and-autophagic-destruction-by-the-mononuclear-phagocyte
#17
Taslima T Lina, Tian Luo, Thangam-Sudha Velayutham, Seema Das, Jere W McBride
In multicellular organisms, autophagy is induced as an innate defense mechanism. Notably, the obligate intracellular bacterium, Ehrlichia chaffeensis, resides in early endosome-like vacuoles and circumvents lysosomal fusion through an unknown mechanism, thereby avoiding destruction in the autophagolysosome. In this study, we reveal that Wnt signaling plays a crucial role in inhibition of lysosomal fusion and autolysosomal destruction of ehrlichiae. During early infection, autophagosomes fuse with ehrlichial vacuoles to form an amphisome indicated by presence of autophagy markers such as LC3, Beclin-1 and p62...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28939105/protein-kinase-c-eta-regulates-mcl-1-level-via-erk1
#18
Deepanwita Pal, Alakananda Basu
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#19
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/28817124/directed-differentiation-and-long-term-maintenance-of-epicardial-cells-derived-from-human-pluripotent-stem-cells-under-fully-defined-conditions
#20
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
keyword
keyword
115967
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"