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https://www.readbyqxmd.com/read/28191677/uvb-represses-melanocyte-cell-migration-and-acts-through-%C3%AE-catenin
#1
Juliette U Bertrand, Valérie Petit, Elke Hacker, Irina Berlin, Nicholas K Hayward, Marie Pouteaux, Evelyne Sage, David C Whiteman, Lionel Larue
The exposure of skin to ultraviolet (UV) radiation can have both beneficial and deleterious effects: it can lead, for instance, to increased pigmentation and vitamin D synthesis but also to inflammation and skin cancer. UVB may induce genetic and epigenetic alterations, and have reversible effects associated with post-translational and gene regulation modifications. β-catenin is a main driver in melanocyte development; although infrequently mutated in melanoma, its cellular localization and activity is frequently altered...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28148649/c3g-shows-regulated-nucleo-cytoplasmic-exchange-and-represses-histone-modifications-associated-with-euchromatin
#2
Dhruv Kumar Shakyawar, Kunal Dayma, Anesh Ramadhas, Chavvakula Varalakshmi, Vegesna Radha
C3G (RapGEF1) is a ubiquitously expressed guanine nucleotide exchange factor that functions in signaling pathways regulating cell proliferation, apoptosis, and actin reorganization. It is essential for differentiation, and early embryonic development in mice. Over-expressed C3G shows predominant cytoplasmic localization, but endogenous C3G is a component of nuclear fractions in a variety of cell types. Co-expression of Importin-α and inhibition of nuclear export by Leptomycin B resulted in predominant nuclear localization of C3G...
February 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#3
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28146408/the-antimalarial-effect-of-curcumin-is-mediated-by-the-inhibition-of-glycogen-synthase-kinase-3%C3%AE
#4
Amatul Hamizah Ali, Suhaini Sudi, Rusliza Basir, Noor Embi, Hasidah Mohd Sidek
Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development...
February 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28126496/glycogen-synthase-kinase-3-beta-alters-anxiety-depression-and-addiction-related-behaviors-and-neuronal-activity-in-the-nucleus-accumbens-shell
#5
Elizabeth J Crofton, Miroslav N Nenov, Yafang Zhang, Federico Scala, Sean A Page, David L McCue, Dingge Li, Jonathan D Hommel, Fernanda Laezza, Thomas A Green
Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats...
January 23, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28114292/gsk3-is-a-metabolic-checkpoint-regulator-in-b-cells
#6
Julia Jellusova, Matthew H Cato, John R Apgar, Parham Ramezani-Rad, Charlotte R Leung, Cindi Chen, Adam D Richardson, Elaine M Conner, Robert J Benschop, James R Woodgett, Robert C Rickert
B cells predominate in a quiescent state until an antigen is encountered, which results in rapid growth, proliferation and differentiation of the B cells. These distinct cell states are probably accompanied by differing metabolic needs, yet little is known about the metabolic control of B cell fate. Here we show that glycogen synthase kinase 3 (Gsk3) is a metabolic sensor that promotes the survival of naive recirculating B cells by restricting cell mass accumulation. In antigen-driven responses, Gsk3 was selectively required for regulation of B cell size, mitochondrial biogenesis, glycolysis and production of reactive oxygen species (ROS), in a manner mediated by the co-stimulatory receptor CD40...
March 2017: Nature Immunology
https://www.readbyqxmd.com/read/28111255/delayed-treatment-of-6-bromoindirubin-3-oxime-stimulates-neurogenesis-and-functional-recovery-after-focal-ischemic-stroke-in-mice
#7
Li-Li Wang, Jimei Li, Xiaohuan Gu, Ling Wei, Shan Ping Yu
Glycogen synthase kinase 3β (GSK3β) was originally identified as a regulator for glycogen metabolism and is now an important therapeutic target for a variety of brain disorders including neurodegenerative diseases due to it's pivotal role in cellular metabolism, proliferation and differentiation. In the development of stroke therapies focusing on tissue repair and functional recovery, promoting neurogenesis is a main approach in regenerative medicine. In the present investigation, we explored the effects of a GSK3β specific inhibitor, 6-Bromoindirubin-3'-oxime (BIO), on regenerative activities of neuroblasts in the subventricular zone (SVZ) and functional recovery after focal cerebral ischemia...
January 19, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28110316/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#8
Liu Xunxian, Yao Zemin
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28107504/sox10-nano-lantern-reporter-human-ips-cells-a-versatile-tool-for-neural-crest-research
#9
Tomoko Horikiri, Hiromi Ohi, Mitsuaki Shibata, Makoto Ikeya, Morio Ueno, Chie Sotozono, Shigeru Kinoshita, Takahiko Sato
The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL) reporter human induced pluripotent stem cells (hiPS) by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021...
2017: PloS One
https://www.readbyqxmd.com/read/28106087/dynamical-states-possibilities-and-propagation-of-stress-signal
#10
Md Zubbair Malik, Shahnawaz Ali, Soibam Shyamchand Singh, Romana Ishrat, R K Brojen Singh
The stress driven dynamics of Notch-Wnt-p53 cross-talk is subjected to a few possible dynamical states governed by simple fractal rules, and allowed to decide its own fate by choosing one of these states which are contributed from long range correlation with varied fluctuations due to active molecular interaction. The topological properties of the networks corresponding to these dynamical states have hierarchical features with assortive structure. The stress signal driven by nutlin and modulated by mediator GSK3 acts as anti-apoptotic signal in this system, whereas, the stress signal driven by Axin and modulated by GSK3 behaves as anti-apoptotic for a certain range of Axin and GSK3 interaction, and beyond which the signal acts as favor-apoptotic signal...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100707/the-rla1-smos1-transcription-factor-functions-with-osbzr1-to-regulate-brassinosteroid-signaling-and-rice-architecture
#11
Shenglong Qiao, Shiyong Sun, Linlin Wang, Zhihua Wu, Chengxiang Li, Xiaoming Li, Tao Wang, Linna Leng, Weisheng Tian, Tiegang Lu, Xuelu Wang
Brassinosteroids (BRs) are plant-specific steroid hormones that control plant growth and development. Recent studies have identified key components of the BR signaling pathway in Arabidopsis thaliana and in rice (Oryza sativa); however, the mechanism of BR signaling in rice, especially downstream of GSK3/SHAGGY-like kinase (GSK2), remains unclear. Here we identified a BR-insensitive rice mutant, reduced leaf angle 1 (rla1), and cloned the corresponding gene. RLA1 was identical to the previously reported SMALL ORGAN SIZE 1 (SMOS1) which was cloned from another allele...
January 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28098160/a-zip6-zip10-heteromer-controls-ncam1-phosphorylation-and-integration-into-focal-adhesion-complexes-during-epithelial-to-mesenchymal-transition
#12
Dylan Brethour, Mohadeseh Mehrabian, Declan Williams, Xinzhu Wang, Farinaz Ghodrati, Sepehr Ehsani, Elizabeth A Rubie, James R Woodgett, Jean Sevalle, Zhengrui Xi, Ekaterina Rogaeva, Gerold Schmitt-Ulms
The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096467/mir-21-mediated-radioresistance-is-via-promoting-repair-of-dna-double-strand-breaks
#13
Baocheng Hu, Xiang Wang, Suofeng Hu, Xiaomin Ying, Ping Wang, Xiangming Zhang, Jian Wang, Hongyan Wang, Ya Wang
MiR-21 as an oncogene that over-expresses in most human tumors involves radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance is through promoting repair of DNA double strand breaks, which includes to facilitate both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ is through targeting GSK3B (a novel target of miR-21) that affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR is through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase since GSK3B promotes degradation of both CDC25A and Cyclin D1, but CDC25A and Cyclin D1 have an opposite effect on HRR...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28094799/activation-of-wnt-%C3%AE-catenin-signalling-via-gsk3-inhibitors-direct-differentiation-of-human-adipose-stem-cells-into-functional-hepatocytes
#14
Jieqiong Huang, Xinyue Guo, Weihong Li, Haiyan Zhang
The generation of hepatocytes that are derived from human adipose stem cells (hASCs) represents an alternative to human hepatocytes for individualized therapeutic and pharmaceutical applications. However, the mechanisms facilitating hepatocyte differentiation from hASCs are not well understood. Here, we show that upon exposure to glycogen synthase kinase 3 (GSK3) inhibitors alone, the expression of definitive endoderm specific genes GATA4, FOXA2, and SOX17 in hASCs significantly increased in a manner with activation of Wnt/β-catenin signalling...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089951/bzr1-positively-regulates-freezing-tolerance-via-cbf-dependent-and-cbf-independent-pathways-in-arabidopsis
#15
Hui Li, Keyi Ye, Yiting Shi, Jinkui Cheng, Xiaoyan Zhang, Shuhua Yang
Cold stress is a major environmental factor that adversely affects plant growth and development. The C-repeat Binding Factor/DRE Binding Factor 1 (CBF/DREB1) transcriptional regulatory cascade has been shown to play important roles in plant response to cold. Here we demonstrate that two key components of BR signaling modulate freezing tolerance of plants. The loss-of-function mutant of the GSK3-like kinases involved in BR signaling, bin2-3 bil1 bil2, showed increased freezing tolerance, whereas overexpression of BIN2 resulted in hypersensitivity to freezing stress under both non-acclimated and acclimated conditions...
January 13, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28081383/inhibiting-effect-of-lithium-chloride-on-endotoxin-induced-uveitis-in-rats
#16
Shuo Yang, Shuo Yu, Xinli Liu, Jinyi Yu, Xiaosheng Zhang, Hong Lu
PURPOSE: To evaluate the anti-inflammatory effect of lithium chloride in endotoxin-induced uveitis. METHODS: A total of 200 Wistar rats were randomly divided into four groups: a control group; EIU group; LiCl-treated control group; and LiCl-treated lipopolysaccharide group. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining were used to determine the degree of inflammatory reaction. Level of glycogen synthase kinase3-beta and nuclear factor-kappa B p65 in iris-ciliary body was examined by western blot and RT-PCR...
January 12, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28077400/differential-expression-of-hedgehog-and-snail-in-cutaneous-fibrosing-disorders-implications-for-targeted-inhibition
#17
Amrita Goyal, Katy R Linskey, Jonathan Kay, Lyn M Duncan, Rosalynn M Nazarian
OBJECTIVES: To examine Hedgehog signaling in cutaneous fibrosing disorders for which effective approved therapies are lacking, expand our knowledge of pathophysiology, and explore the rationale for targeted inhibition. METHODS: Stain intensity and percentage of cells staining for Sonic hedgehog (Shh), Indian hedgehog (Ihh), Patched (Ptch), glycogen synthase kinase 3 β (GSK3-β), β-catenin, and Snail were evaluated in human skin biopsy specimens of keloid, hypertrophic scar (Hscar), scleroderma, nephrogenic systemic fibrosis (NSF), scar, and normal skin using a tissue microarray...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#18
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28068632/hydroxysafflor-yellow-a-cardioprotection-in-ischemia-reperfusion-i-r-injury-mainly-via-akt-hexokinase-ii-independent-of-erk-gsk-3%C3%AE-pathway
#19
Jia Min, Cui Wei
Hydroxysafflor yellow A (HSYA) is the main active component of Carthamus tinctorius L which has been used for hundreds of years in Chinese folk medicine in the treatment cardiovascular disease. This study was designed to investigate whether HSYA exerts cardioprotection in ischemia-reperfusion (I/R) injury heart and the mechanisms involved. The protective effect and mechanisms in myocardial ischemia reperfusion injury of HSYA was evaluated by hypoxia-recover (H/R) injury cell model which induced by hypoxia and recovered with oxygen in H9c2 cells...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28068511/inhibition-of-glycogen-synthase-kinase-3-accelerated-liver-regeneration-after-acetaminophen-induced-hepatotoxicity-in-mice
#20
Bharat Bhushan, Samikshya Poudel, Michael W Manley, Nairita Roy, Udayan Apte
Overdose of acetaminophen (APAP) is the leading cause of acute liver failure (ALF) in the United States. Timely initiation of compensatory liver regeneration after APAP hepatotoxicity is critical for final recovery, but the mechanisms of liver regeneration after APAP-induced ALF have not been extensively explored yet. Previous studies from our laboratory have demonstrated that activation of β-catenin signaling after APAP overdose is associated with timely liver regeneration. Herein, we investigated the role of glycogen synthase kinase 3 (GSK3) in liver regeneration after APAP hepatotoxicity using a pharmacological inhibition strategy in mice...
January 6, 2017: American Journal of Pathology
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