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https://www.readbyqxmd.com/read/29134466/glycogen-synthase-kinase-3%C3%AE-mediated-regulation-of-matrix-metalloproteinase-9-and-its-involvement-in-oral-squamous-cell-carcinoma-progression-and-invasion
#1
Kamdeo K Pramanik, Siddavaram Nagini, Abhay K Singh, Prajna Mishra, Tanushree Kashyap, Nidhi Nath, Manzar Alam, Ajay Rana, Rajakishore Mishra
PURPOSE: Oral squamous cell carcinoma (OSCC)-related deaths mainly result from invasion of the tumor cells into local cervical lymph nodes. It has been reported that progressive basement membrane loss promotes the metastatic and invasive capacities of OSCCs. Matrix metalloproteinase-9 (MMP-9) is known to play a central role in tumor progression and invasion. However, the role of MMP-9 in OSCC invasion has so far remained paradoxical and little is known about its regulation. Here, we aimed to assess MMP-9 expression regulation and its activation by glycogen synthase kinase-3β during human OSCC progression and invasion...
November 13, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29133865/cold-acclimation-causes-fiber-type-specific-responses-in-glucose-and-fat-metabolism-in-rat-skeletal-muscles
#2
Diane M Sepa-Kishi, Yass Sotoudeh-Nia, Ayesha Iqbal, George Bikopoulos, Rolando B Ceddia
This study investigated fiber type-specific metabolic responses and the molecular mechanisms that regulate glucose and fat metabolism in oxidative and glycolytic muscles upon cold acclimation. Male Wistar rats were exposed to cold (4 °C) for 7 days, and then glycogen synthesis and content, glucose and palmitate oxidation, and the molecular mechanisms underlying these metabolic pathways were assessed in soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles. Cold acclimation increased glycogen synthesis, glycogen content, glucose oxidation, and reduced glycogen synthase (GS) phosphorylation only in Sol muscles...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132997/thyroid-hormone-improves-insulin-signaling-and-reduces-the-activation-of-neurodegenerative-pathway-in-the-hippocampus-of-diabetic-adult-male-rats
#3
Fernanda Prieto-Almeida, Ana Carolina Panveloski-Costa, Fernanda Crunfli, Silvania da Silva Teixeira, Maria Tereza Nunes, Andréa da Silva Torrão
AIMS: Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system...
November 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/29131712/how-rice-glycogen-synthase-kinase-like-5-osgsk5-integrates-salinity-stress-response-to-source-sink-adaptation-a-proposed-model
#4
Maysaya Thitisaksakul, Shaoyun Dong, Diane M Beckles
We have previously shown that overexpression of GSK3-like kinase 5 in rice (OsGSK5) was associated with higher starch accumulation and better growth under severe salinity stress. Short-term (14)CO2 feeding experiments suggested that OsGSK5 promoted higher flux to starch accumulation in the roots under this condition and that this mechanism may help to underscore the better growth characteristics observed. Here, we expand upon this hypothesis and consider (i) how OsGSK5 action could fit into a signaling model that integrates salinity stress to changes in starch metabolism, and (ii) how this would facilitate whole plant physiological adaptions in source-to-sink partitioning...
November 13, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29121589/pharmacological-targeting-of-gsk-3-and-nrf2-provides-neuroprotection-in-a-preclinical-model-of-tauopathy
#5
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29119099/wnt-and-hedgehog-signaling-regulate-the-differentiation-of-f9-cells-into-extraembryonic-endoderm
#6
Gurjoth S J Deol, Tina N Cuthbert, Mohamed I Gatie, Danielle M Spice, Lindsay R Hilton, Gregory M Kelly
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) when treated with retinoic acid (RA), and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh) and a subset of its target genes through Gli activation during PrE induction...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29102676/a-partnership-with-the-proteasome-the-destructive-nature-of-gsk3
#7
REVIEW
Holly Robertson, John D Hayes, Calum Sutherland
Glycogen Synthase Kinase-3 (GSK3) was originally reported as a key enzyme of glucose homeostasis through regulation of the rate of glycogen synthesis. It has subsequently been found to influence most cellular processes, including growth, differentiation and death, as part of its role in modulating response to hormonal, nutritional and cellular stress stimuli. More than 100 protein targets for GSK3 have been proposed although only a small fraction of these have been convincingly validated in physiological cell systems...
November 1, 2017: Biochemical Pharmacology
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
#8
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/29053582/zinc-supplementation-improves-glucose-homeostasis-in-high-fat-fed-mice-by-enhancing-pancreatic-%C3%AE-cell-function
#9
Vinícius Cooper-Capetini, Diogo Antonio Alves de Vasconcelos, Amanda Roque Martins, Sandro Massao Hirabara, José Donato, Angelo Rafael Carpinelli, Fernando Abdulkader
Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and β-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl₂ (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl₂ (HFZ)...
October 20, 2017: Nutrients
https://www.readbyqxmd.com/read/29030569/active-gsk3%C3%AE-and-an-intact-%C3%AE-catenin-tcf-complex-are-essential-for-the-differentiation-of-human-myogenic-progenitor-cells
#10
C C Agley, F C Lewis, O Jaka, N R Lazarus, C Velloso, P Francis-West, G M Ellison-Hughes, S D R Harridge
Wnt-β-catenin signalling is essential for skeletal muscle myogenesis during development, but its role in adult human skeletal muscle remains unknown. Here we have used human primary CD56(Pos) satellite cell-derived myogenic progenitors obtained from healthy individuals to study the role of Wnt-β-catenin signalling in myogenic differentiation. We show that dephosphorylated β-catenin (active-β-catenin), the central effector of the canonical Wnt cascade, is strongly upregulated at the onset of differentiation and undergoes nuclear translocation as differentiation progresses...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024409/the-natural-agent-rhein-induces-%C3%AE-catenin-degradation-and-tumour-growth-arrest
#11
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
#12
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
#13
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
#14
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/28984836/balanced-diet-fed-fat-1-transgenic-mice-exhibit-lower-hindlimb-suspension-induced-soleus-muscle-atrophy
#15
Gabriel Nasri Marzuca-Nassr, Gilson Masahiro Murata, Amanda Roque Martins, Kaio Fernando Vitzel, Amanda Rabello Crisma, Rosângela Pavan Torres, Jorge Mancini-Filho, Jing Xuan Kang, Rui Curi
The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle...
October 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28964663/saffron-crocus-sativus-intake-provides-nutritional-preconditioning-against-myocardial-ischemia-reperfusion-injury-in-wild-type-and-apoe-mice-involvement-of-nrf2-activation
#16
P Efentakis, A Rizakou, E Christodoulou, A Chatzianastasiou, M G López, R León, E Balafas, N P E Kadoglou, I Tseti, H Skaltsa, N Kostomitsopoulos, E K Iliodromitis, G Valsami, I Andreadou
BACKGROUND AND AIMS: Saffron is an antioxidant herbal derivative; however, its efficacy as a nutritional cardioprotective agent has not been fully elucidated. We investigated the cardioprotective properties of a standardized saffron aqueous extract (SFE) against ischemia/reperfusion (I/R) injury in Wild-Type (WT) and ApoE((-/-)) mice and the underlying molecular mechanisms. METHODS AND RESULTS: WT and ApoE((-/-)) mice were subjected to 30 min I and 2 h R, with the following per os interventions for 4 weeks: 1) WT Control Group, receiving Water for Injection (WFI); 2) WT Crocus Group, receiving SFE at a dose of 60 mg/kg/day; 3) WT Crocus + Wort group, receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus 15 min before R; 4) ApoE((-/-)) Control Group, receiving WFI; 5) ApoE((-/-)) Crocus Group, receiving SFE at a dose of 60 mg/kg/day and 6) ApoE((-/-)) Crocus + Wort: receiving SFE as described above and wortmannin at a dose of 60 μg/kg bolus, 15 min before R...
October 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28939105/protein-kinase-c-eta-regulates-mcl-1-level-via-erk1
#17
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/28935982/glycogen-synthase-kinase-3%C3%AE-inhibition-links-mitochondrial-dysfunction-extracellular-matrix-remodelling-and-terminal-differentiation-in-chondrocytes
#18
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
#19
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
#20
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)
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