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glycogen synthase kinase

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https://www.readbyqxmd.com/read/27918305/tuberous-sclerosis-complex-inactivation-disrupts-melanogenesis-via-mtorc1-activation
#1
Juxiang Cao, Magdalena E Tyburczy, Joel Moss, Thomas N Darling, Hans R Widlund, David J Kwiatkowski
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1). Patients with TSC develop hypomelanotic macules (white spots), but the molecular mechanisms underlying their formation are not fully characterized. Using human primary melanocytes and a highly pigmented melanoma cell line, we demonstrate that reduced expression of either TSC1 or TSC2 causes reduced pigmentation through mTORC1 activation, which results in hyperactivation of glycogen synthase kinase 3β (GSK3β), followed by phosphorylation of and loss of β-catenin from the nucleus, thereby reducing expression of microphthalmia-associated transcription factor (MITF), and subsequent reductions in tyrosinase and other genes required for melanogenesis...
December 5, 2016: Journal of Clinical Investigation
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
#2
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/27907035/exendin-4-inhibits-hepatic-lipogenesis-by-increasing-%C3%AE-catenin-signaling
#3
Mi Hae Seo, Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won-Young Lee
The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours...
2016: PloS One
https://www.readbyqxmd.com/read/27904664/tauroursodeoxycholic-acid-inhibits-endoplasmic-reticulum-stress-blocks-mitochondrial-permeability-transition-pore-opening-and-suppresses-reperfusion-injury-through-gsk-3%C3%A3-in-cardiac-h9c2-cells
#4
Yuxi Xie, Yonggui He, Zhiliang Cai, Jianhang Cai, Mengyao Xi, Yidong Zhang, Jinkun Xi
This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H2O2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904257/expression-of-p38-mitogen-activated-protein-kinases-glycogen-synthase-kinase-c-jun-nh2-terminal-kinase-extracellular-signal-regulated-kinase-signaling-can-it-be-used-as-molecular-markers-among-trauma-hemorrhagic-shock-patients
#5
Manoj Kumar, Keshava Sharma, Sanjeev Bhoi, Mahendra Kumar, Manjunath Maruti Pol
No abstract text is available yet for this article.
October 2016: Journal of Emergencies, Trauma, and Shock
https://www.readbyqxmd.com/read/27902447/a-unique-type-of-gsk-3-inhibitor-brings-new-opportunities-to-the-clinic
#6
Avital Licht-Murava, Rom Paz, Lilach Vaks, Limor Avrahami, Batya Plotkin, Miriam Eisenstein, Hagit Eldar-Finkelman
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimer's disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27902446/science-signaling-podcast-for-15-november-2016-a-new-type-of-kinase-inhibitor
#7
Hagit Eldar-Finkelman, Annalisa M VanHook
This Podcast features an interview with Hagit Eldar-Finkelman, author of a Research Article that appears in the 15 November 2016 issue of Science Signaling, about a newly developed inhibitor of glycogen synthase kinase 3 (GSK-3). GSK-3 participates in several signaling networks and has been implicated in various pathologies, including neurodegenerative diseases, cognitive impairments, and cancer. Licht-Murava et al developed L807mts, a substrate-competitive peptide inhibitor that blocks GSK-3 activity through an unusual mechanism...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27896249/glycogen-synthase-kinase-3%C3%AE-and-cyclin-d1-expression-in-cervical-carcinogenesis
#8
Hyunsoo Park, Myunghwa Lee, Dae Woon Kim, Seo Yoo Hong, Hojung Lee
OBJECTIVE: Glycogen synthase kinase 3β (GSK3β) is a pluripotent protein kinase involved in the development of cancers through regulation of numerous oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase transition in various cells, is one of target proteins that GSK3β regulate. Our objective was to assess the expression of GSK3β and cyclin D1 in cervical neoplasm of different histologic grades and to identify their correlation in cervical carcinogenesis. METHODS: Immunohistochemical analysis of GSK3β and cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers including 56 squamous cell carcinomas and 7 adenocarcinomas...
November 2016: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/27894404/streptozotocin-induces-neurite-outgrowth-via-pi3k-akt-and-glycogen-synthase-kinase-3%C3%AE-in-neuro2a-cells
#9
T Nishimoto, R Kimura, A Matsumoto, H Sugimoto
Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner. STZ also had the same neurite outgrowth-inducing activity as that of retinoic acid (RA), which is well known neurite outgrowth inducer...
October 31, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27888450/effects-of-chromium-loaded-chitosan-nanoparticles-on-glucose-transporter-4-relevant-mrna-and-proteins-of-phosphatidylinositol-3-kinase-akt2-kinase-and-amp-activated-protein-kinase-of-skeletal-muscles-in-finishing-pigs
#10
Lujie Liu, Bin Wang, Yudan He, Wenjing Tao, Zixun Liu, Minqi Wang
The study was conducted to evaluate the effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on glucose transporter 4 (GLUT4), relevant messenger RNA (mRNA), and proteins involved in phosphatidylinositol 3-kinase (PI3K), Akt2-kinase, and AMP-activated protein kinase (AMPK) of skeletal muscles in finishing pigs. A total of 120 crossbred barrows (BW 65.00 ± 1.26 kg) were randomly allotted to four dietary treatments, with three pens per treatment and 10 pigs per pen. Pigs were fed the basal diet supplemented with 0, 100, 200, or 400 μg/kg of Cr from Cr-CNP for 35 days...
November 25, 2016: Biological Trace Element Research
https://www.readbyqxmd.com/read/27882154/kai-xin-san-a-traditional-chinese-medicine-formulation-exerts-antidepressive-and-neuroprotective-effects-by-promoting-pcreb-upstream-pathways
#11
Xian-Zhe Dong, Dong-Xiao Wang, Bing-Ying Yu, Ping Liu, Yuan Hu
Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS...
November 2016: Experimental and Therapeutic Medicine
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
#12
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/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#13
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27876551/stressed-and-inflamed-can-gsk3-be-blamed
#14
REVIEW
Richard S Jope, Yuyan Cheng, Jeffrey A Lowell, Ryan J Worthen, Yoel H Sitbon, Eleonore Beurel
Psychological stress has a pervasive influence on our lives. In many cases adapting to stress strengthens organisms, but chronic or severe stress is usually harmful. One surprising outcome of psychological stress is the activation of an inflammatory response that resembles inflammation caused by infection or trauma. Excessive psychological stress and the consequential inflammation in the brain can increase susceptibility to psychiatric diseases, such as depression, and impair learning and memory, including in some patients with cognitive deficits...
November 19, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27876112/antioxidant-defense-of-nrf2-vs-pro-inflammatory-system-of-nf-%C3%AE%C2%BAb-during-the-amoebic-liver-infection-in-hamster
#15
Liseth R Aldaba-Muruato, Martin H Muñoz-Ortega, María Del R Campos-Esparza, José R Macías-Pérez, Nayeli A Márquez-Muñoz, Ana G Villalobos-Santos, Javier Ventura-Juárez
Entamoeba histolytica is the causative agent of amoebic liver abscess (ALA), which course with an uncontrolled inflammation and nitro-oxidative stresses, although it is well known that amoeba has an effective defence mechanisms against this toxic environment, the underlying molecular factors responsible for progression of tissue damage remain largely unknown. The purpose of the present study was to determine during the acute stage of ALA in hamsters, the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappa B (NF-κB), which are activated in response to oxidative stress...
November 23, 2016: Parasitology
https://www.readbyqxmd.com/read/27875297/glycogen-synthase-kinase-3-gsk-3-mediated-phosphorylation-of-uracil-n-glycosylase-2-ung2-facilitates-repair-of-floxuridine-induced-dna-lesions-and-promotes-cell-survival
#16
Carly A Baehr, Catherine J Huntoon, Song-My Hoang, Calvin R Jerde, Larry M Karnitz
Uracil N-glycosylase 2 (UNG2), the nuclear isoform of UNG, catalyzes the removal of uracil or 5-fluorouracil lesions that accumulate in DNA following treatment with the anti-cancer agents 5-fluorouracil and 5-fluorodeoxyuridine (floxuridine), a 5-fluorouracil metabolite. By repairing these DNA lesions before they can cause cell death, UNG2 promotes cancer cell survival and is therefore critically involved in tumor resistance to these agents. However, the mechanisms by which UNG2 is regulated remain unclear...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27866373/involvement-of-gsk-3%C3%AE-phosphorylation-through-pi3-k-akt-in-cerebral-ischemia-induced-neurogenesis-in-rats
#17
Keishi Kisoh, Hideki Hayashi, Tsuyoshi Itoh, Mayumi Asada, Miho Arai, Bo Yuan, Kouichi Tanonaka, Norio Takagi
Glycogen synthase kinase (GSK)-3β, which is abundantly expressed in the central nervous system, regulates various cellular processes including gene expression, cell proliferation, and differentiation. However, involvement of GSK-3β in cerebral ischemia-induced endogenous neurogenesis is not yet fully understood. Appropriate strategies to prevent ischemic cell damage and subsequent severe sequelae are needed. The purpose of the present study was to determine the relationship between pathophysiological alteration of the GSK-3β signaling pathway and cerebral ischemia-induced endogenous neurogenesis in rats...
November 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27864906/role-and-regulation-of-glycogen-synthase-kinase-3-beta-in-bovine-spermatozoa
#18
Michael Belenky, Haim Breitbart
The serine/threonine kinase Glycogen synthase kinase 3 (GSK-3) is a master switch that regulates a multitude of cellular pathways, including the acrosome reaction in sperm. In epididymal sperm cells, for example, GSK-3 activity correlates with inhibition of motility-yet no direct pathways connecting GSK-3 activation with loss of motility have been described. Indeed, the details of how GSK-3 is regulated during sperm capacitation and the acrosome reaction remains obscure. To this end, we addressed the involvement of the GSK-3 beta isoform in several known pathways that contribute to motility and the acrosome reaction...
November 19, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27863213/tubular-cytoplasmic-expression-of-snai1-in-renal-transplant-biopsies-a-sign-of-diseased-epithelial-phenotype
#19
Marco Prunotto, Lyubov Chaykovska, Massimo Bongiovanni, Milo Frattini, Thomas Cagarelli, Franziska Weibel, Maurizio Bruschi, Antonio Garcia de Herreros, Solange Moll
The aim of the present study was to analyze in vivo the role of SNAI1 on renal fibrosis. Unilateral ureteral obstruction injury was induced in Snai1 knockout mice. Snai1 gene deletion was, however, only partial and could therefore not be correlated to reduced fibrosis. Expression of SNAI1 protein and epithelial-mesenchymal transformation markers was then assessed in human chronic allograft nephropathy biopsy specimens. Significant up-regulation of SNAI1 protein was detected within cytoplasm of proximal tubules localized, for some of them, near foci of fibrosis and tubular atrophy...
November 15, 2016: American Journal of Pathology
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
#20
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
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