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glycogen synthase kinase

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https://www.readbyqxmd.com/read/29777057/glycogen-synthase-kinase-3-gsk-3-activity-regulates-mrna-methylation-in-mouse-embryonic-stem-cells
#1
Kelsie J Faulds, Jennifer N Egelston, Laura J Sedivy, Matthew K Mitchell, Sanjana Garimella, Hanna Kozlowski, Angelo D'Alessandro, Kirk C Hansen, Jeremy L Balsbaugh, Christopher J Phiel
Glycogen synthase kinase-3 (Gsk-3) activity regulates multiple signal transduction pathways, and is also a key component of the network responsible for maintaining stem cell pluripotency. Genetic deletion of Gsk-3α and Gsk-3β or inhibition of Gsk-3 activity via small molecules promotes stem cell pluripotency, yet the mechanism underlying the role for Gsk-3 in this process remains ambiguous. Another cellular process that has been shown to affect stem cell pluripotency is mRNA methylation (m6 A). Here, we describe an intersection between these components - the regulation of m6 A by Gsk-3...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29775963/brain-ischemic-preconditioning-protects-against-ischemic-injury-and-preserves-the-blood-brain-barrier-via-oxidative-signaling-and-nrf2-activation
#2
Tuo Yang, Yang Sun, Leilei Mao, Meijuan Zhang, Qianqian Li, Lili Zhang, Yejie Shi, Rehana K Leak, Jun Chen, Feng Zhang
Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199)...
May 6, 2018: Redox Biology
https://www.readbyqxmd.com/read/29775701/lithium-posttreatment-alleviates-blood-brain-barrier-injury-after-intracerebral-hemorrhage-in-rats
#3
Weishan Li, Rui Li, Sha Zhao, Cheng Jiang, Zhen Liu, Xiaobo Tang
Vasogenic cerebral edema formation after blood brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). The present study aims to probe into a therapeutic method on BBB preservation after ICH with a glycogen synthase kinase-3β (GSK-3β) inhibitor, lithium. Intrastriatal infusion of semicoagulated autologous whole blood or sham surgery was performed on male Sprague-Dawley (SD) rats (n = 208).Experimental animals received administration of 4,6-disubstitutedpyrrolo-pyrimidine (TWS119), lithium alone or in combination with a phosphatidylinositol 3-kinase inhibitor, wortmannin, after ICH...
May 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29773710/arginine-methylation-is-required-for-canonical-wnt-signaling-and-endolysosomal-trafficking
#4
Lauren V Albrecht, Diego Ploper, Nydia Tejeda-Muñoz, Edward M De Robertis
Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications...
May 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#5
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29766503/transcriptome-analysis-of-potential-mirna-involved-in-adipogenic-differentiation-of-c2c12-myoblasts
#6
Ye Hou, Liangliang Fu, Jingjin Li, Jingxuan Li, Yunxia Zhao, Yu Luan, An Liu, Huiying Liu, Xinyun Li, Shuhong Zhao, Changchun Li
>Emerging evidence indicates that microRNA (miRNA) plays an important role in adipogenesis and disease pathogenesis. To investigate the miRNA involved in regulating different periods of adipogenesis, we performed a comprehensive study on microRNAome during the stimulation of adipogenesis by an adipogenic differentiation cocktail in C2C12 myoblasts at 0, 2, 4, and 7 days using the Solexa sequencing technology. In this study, we identified 52 differentially expressed (DE) miRNA. Functional annotation indicated that the target genes of DE miRNA were mostly enriched in adipogenic transdifferentiation and fat metabolism-related pathways, including Wnt, mitogen-activated protein kinase (MAPK), and insulin signaling...
May 16, 2018: Lipids
https://www.readbyqxmd.com/read/29765214/tiotropium-inhibits-methacholine-induced-extracellular-matrix-production-via-%C3%AE-catenin-signaling-in-human-airway-smooth-muscle-cells
#7
Yating Huo, Lili Guan, Jiawen Xu, Luqian Zhou, Rongchang Chen
Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29763645/agmatine-potentiates-neuroprotective-effects-of-subthreshold-concentrations-of-ketamine-via-mtor-s6-kinase-signaling-pathway
#8
Mauren K Tavares, Suellen Dos Reis, Nicolle Platt, Isabella A Heinrich, Ingrid A V Wolin, Rodrigo B Leal, Manuella P Kaster, Ana Lúcia S Rodrigues, Andiara E Freitas
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug...
May 12, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29761559/conditional-depletion-of-gsk3b-protects-oligodendrocytes-from-apoptosis-and-lessens-demyelination-in-the-acute-cuprizone-model
#9
Bin Xing, Lauren E Brink, Kelly Maers, Mara L Sullivan, Richard J Bodnar, Donna B Stolz, Franca Cambi
Apoptosis is recognized as the main mechanism of oligodendrocyte loss in Multiple Sclerosis caused either by immune mediated injury (Barnett & Prineas, ) or a direct degenerative process (oligodendrogliapathy; Lucchinetti et al., ). Cuprizone induced demyelination is the result of non-immune mediated apoptosis of oligodendrocytes (OL) and represents a model of oligodendrogliapathy (Simmons, Pierson, Lee, & Goverman, ). Glycogen Synthase Kinase (GSK) 3b has been shown to be pro-apoptotic for cells other than OL...
May 15, 2018: Glia
https://www.readbyqxmd.com/read/29760875/glycogen-synthase-kinase-3-promotes-multicellular-development-over-unicellular-encystation-in-encysting-dictyostelia
#10
Yoshinori Kawabe, Takahiro Morio, Yoshimasa Tanaka, Pauline Schaap
Background: Glycogen synthase kinase 3 (GSK3) regulates many cell fate decisions in animal development. In multicellular structures of the group 4 dictyostelid Dictyostelium discoideum , GSK3 promotes spore over stalk-like differentiation. We investigated whether, similar to other sporulation-inducing genes such as cAMP-dependent protein kinase (PKA), this role of GSK3 is derived from an ancestral role in encystation of unicellular amoebas. Results: We deleted GSK3 in Polysphondylium pallidum , a group 2 dictyostelid which has retained encystation as an alternative survival strategy...
2018: EvoDevo
https://www.readbyqxmd.com/read/29758318/proteome-and-behavioral-alternations-in-phosphorylation-deficient-mutant-collapsin-response-mediator-protein2-knock-in-mice
#11
Haruko Nakamura, Aoi Takahashi-Jitsuki, Hiroko Makihara, Tetsuya Asano, Yayoi Kimura, Jun Nakabayashi, Naoya Yamashita, Yuko Kawamoto, Fumio Nakamura, Toshio Ohshima, Hisashi Hirano, Fumiaki Tanaka, Yoshio Goshima
CRMP2, alternatively designated as DPYSL2, was the first CRMP family member to be identified as an intracellular molecule mediating the signaling of the axon guidance molecule Semaphorin 3A (Sema3A). In Sema3A signaling, cyclin-dependent kinase 5 (Cdk5) primarily phosphorylates CRMP2 at Ser522. Glycogen synthase kinase-3β (GSK-3β) subsequently phosphorylates the residues of Thr509 and Thr514 of CRMP2. Previous studies showed that CRMP2 is involved in pathogenesis of neurological disorders such as Alzheimer's disease...
May 11, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29757923/the-antimalarial-drug-artesunate-attenuates-cardiac-injury-in-a-rodent-model-of-myocardial-infarction
#12
Areeg I Khan, Amar Kapoor, Jianmin Chen, Lukas Martin, Mara Rogazzo, Thomas Mercier, Laurent Decosterd, Massimo Collino, Christoph Thiemermann
Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v.) and patients with severe malaria (2.4 mg/kg i.v.). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA...
June 2018: Shock
https://www.readbyqxmd.com/read/29755479/lysophosphatidylcholine-promotes-phagosome-maturation-and-regulates-inflammatory-mediator-production-through-the-protein-kinase-a-phosphatidylinositol-3-kinase-p38-mitogen-activated-protein-kinase-signaling-pathway-during-mycobacterium-tuberculosis-infection
#13
Hyo-Ji Lee, Hyun-Jeong Ko, Dong-Kun Song, Yu-Jin Jung
Tuberculosis is caused by the infectious agent Mycobacterium tuberculosis (Mtb). Mtb has various survival strategies, including blockade of phagosome maturation and inhibition of antigen presentation. Lysophosphatidylcholine (LPC) is a major phospholipid component of oxidized low-density lipoprotein and is involved in various cellular responses, such as activation of second messengers and bactericidal activity in neutrophils. In this study, macrophages were infected with a low infectious dose of Mtb and treated with LPC to investigate the bactericidal activity of LPC against Mtb...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754289/the-novel-adipokine-wisp1-associates-with-insulin-resistance-and-impairs-insulin-action-in-human-myotubes-and-mouse-hepatocytes
#14
Tina Hörbelt, Christopher Tacke, Mariya Markova, Daniella Herzfeld de Wiza, Frederique Van de Velde, Marlies Bekaert, Yves Van Nieuwenhove, Silke Hornemann, Maria Rödiger, Nicole Seebeck, Elisabeth Friedl, Wenke Jonas, G Hege Thoresen, Oliver Kuss, Anke Rosenthal, Volker Lange, Andreas F H Pfeiffer, Annette Schürmann, Bruno Lapauw, Natalia Rudovich, Olga Pivovarova, D Margriet Ouwens
AIMS/HYPOTHESIS: Wingless-type (Wnt) inducible signalling pathway protein-1 (WISP1) has been recently identified as a proinflammatory adipokine. We examined whether WISP1 expression and circulating levels are altered in type 2 diabetes and whether WISP1 affects insulin signalling in muscle cells and hepatocytes. METHODS: Serum and visceral adipose tissue (VAT) biopsies, for analysis of circulating WISP1 levels by ELISA and WISP1 mRNA expression by real-time quantitative RT-PCR, were collected from normal-weight men (control group, n = 33) and obese men with (n = 46) and without type 2 diabetes (n = 56) undergoing surgery...
May 12, 2018: Diabetologia
https://www.readbyqxmd.com/read/29753867/topiramate-mitigates-3-nitropropionic-acid-induced-striatal-neurotoxicity-via-modulation-of-ampa-receptors
#15
Heba N Shalaby, Dalia M El-Tanbouly, Hala F Zaki
Prevalence of glutamate receptor subunit 2 (GluR2)-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TPM) is a structurally novel anticonvulsant with a well-known modulatory effects on AMPA/kainate subtypes of glutamate receptors. The present study aimed at investigating the neuroprotective potential of TPM on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease-like symptoms...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29753049/antidepressant-effects-of-creatine-on-amyloid-%C3%AE-1-40-treated-mice-the-role-of-gsk-3%C3%AE-nrf-2-pathway
#16
Julia M Rosa, Francis L Pazini, Mauricio P Cunha, André R S Colla, Luana M Manosso, Gianni Mancini, Ana Cristina G Souza, Andreza F de Bem, Rui Daniel Prediger, Ana Lúcia S Rodrigues
Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neuronal lost in specific brain areas including hippocampus, resulting in memory/learning deficits and cognitive impairments. In addition, non-cognitive symptoms are reported in AD patients, such as anxiety, apathy and depressed mood. The current antidepressant drugs present reduced efficacy to improve depressive symptoms in AD patients. Here, we investigated the ability of creatine, a compound with neuroprotective and antidepressant properties, to counteract amyloid β1-40 peptide-induced depressive-like behavior in mice...
May 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29751783/antiproliferative-and-apoptotic-effect-of-ly2090314-a-gsk-3-inhibitor-in-neuroblastoma-in-vitro
#17
Selvi Kunnimalaiyaan, Victoriana K Schwartz, Iris Alao Jackson, T Clark Gamblin, Muthusamy Kunnimalaiyaan
BACKGROUND: Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment. METHODS: The effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29749479/effect-of-combined-chondroitinase-abc-and-hyperbaric-oxygen-therapy-in-a-rat-model-of-spinal-cord-injury
#18
Xiaoyang Liu, Jiefeng Wang, Guangkuo Li, Honglin Lv
The present study aimed to investigate the effect of combined hyperbaric oxygen (HBO) and chondroitinase ABC (ChABC) enzyme therapy in a rat model of spinal cord injury (SCI) and to explore the underlying mechanisms. A total of 48 healthy male Wistar rats were randomly divided into six groups: Sham, SCI, vehicle, HBO, ChABC enzyme and HBO + ChABC. Excluding the sham group, SCI was established in rats by a clip compression injury and rats subsequently received HBO treatment for 2 weeks with or without an intraspinal injection of 0...
April 26, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29749471/gsk3%C3%AE-%C3%A2-mediated-ser156-phosphorylation-modulates-a-bh3%C3%A2-like-domain-in-bcl2l12-during-tmz%C3%A2-induced-apoptosis-and-autophagy-in-glioma-cells
#19
Cheng-Wei Chu, Ming-Chang Yang, Chia-Hua Chou, Wen-Sheng Huang, Bo-Xiu Hsiao, Yeng-Tseng Wang, Shean-Jaw Chiou, Joon-Khim Loh, Yi-Ren Hong
BH3 domains, classified initially as BCL2 homology domains, participate in both apoptosis and autophagy. Beclin‑1 contains a BH3 domain, which is required for binding to antiapoptotic BCL2 homologs and BCL2‑mediated inhibition of autophagy. BCL2‑like 12 (BCL2L12) also harbors a BH3‑like domain, which is 12 residues long and contains a LXXXAE/D motif. In a yeast two‑hybrid system performed in the present study, BCL2L12 shared similar binding partnerships to antiapoptotic BCL2 homologs, such as Beclin‑1...
May 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29749377/p2rx7-mapk1-2-sp1-axis-inhibits-mtor-independent-hspb1-mediated-astroglial-autophagy
#20
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
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