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https://www.readbyqxmd.com/read/28419994/degradation-of-mcl-1-through-gsk-3%C3%AE-activation-regulates-apoptosis-induced-by-bufalin-in-non-small-cell-lung-cancer-h1975-cells
#1
Xiao-Hong Kang, Jing-Hang Zhang, Qing-Qin Zhang, Yan-Hui Cui, Ying Wang, Wei-Zheng Kou, Zhan-Hui Miao, Ping Lu, Li-Fang Wang, Zhen-Ye Xu, Fei Cao
BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#2
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417055/potential-involvement-of-glycogen-synthase-kinase-gsk-3%C3%AE-in-a-rat-model-of-multiple-sclerosis-evidenced-by-lithium-treatment
#3
Meejung Ahn, Jeongtae Kim, Changnam Park, Jinhee Cho, Youngheun Jee, Kyungsook Jung, Changjong Moon, Taekyun Shin
Glycogen synthase kinase (GSK)-3β has been known as a pro-inflammatory molecule in neuroinflammation. The involvement of GSK-3β remains unsolved in acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of this study was to evaluate a potential role of GSK-3β in central nervous system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment significantly delayed the onset of EAE paralysis and ameliorated its severity. Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis factor a but not that of interleukin 10...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416463/glucocorticoids-activate-a-synapse-weakening-pathway-culminating-in-tau-phosphorylation-in-the-hippocampus
#4
Jee Hyun Yi, Christopher Brown, Garry Whitehead, Thomas Piers, Young Seok Lee, Celia Martinez Perez, Philip Regan, Daniel J Whitcomb, Kwangwook Cho
Evidence suggests that the stress hormones glucocorticoids (GCs) can cause cognitive deficits and neurodegeneration. Previous studies have found GCs facilitate physiological synapse weakening, termed long-term depression (LTD), though the precise mechanisms underlying this are poorly understood. Here we show that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse weakening signals. Critically, this ultimately leads to phosphorylation of the microtubule associated protein tau, specifically at the serine 396 residue, and this is a causal factor in the GC-mediated impairment of synaptic function...
April 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28393933/epcam-intracellular-domain-promotes-porcine-cell-reprogramming-by-upregulation-of-pluripotent-gene-expression-via-beta-catenin-signaling
#5
Tong Yu, Yangyang Ma, Huayan Wang
Previous study showed that expression of epithelial cell adhesion molecule (EpCAM) was significantly upregulated in porcine induced pluripotent stem cells (piPSCs). However, the regulatory mechanism and the downstream target genes of EpCAM were not well investigated. In this study, we found that EpCAM was undetectable in fibroblasts, but highly expressed in piPSCs. Promoter of EpCAM was upregulated by zygotic activated factors LIN28, and ESRRB, but repressed by maternal factors OCT4 and SOX2. Knocking down EpCAM by shRNA significantly reduced the pluripotent gene expression...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381424/gsk-3-mediated-phosphorylation-couples-er-golgi-transport-and-nuclear-stabilisation-of-the-creb-h-transcription-factor-to-mediate-apolipoprotein-secretion
#6
Sónia Barbosa, Suzanne Carreira, Peter O'Hare
CREB-H, an ER-anchored transcription factor plays a key role in regulating secretion in metabolic pathways, particularly triglyceride homeostasis. It controls the production both of secretory pathway components and cargoes including apolipoproteins ApoA-IV and ApoC-II, contributing to VLDL/HDL distribution and lipolysis. The key mechanism controlling CREB-H activity involves its ER retention and forward transport to the Golgi, where it is cleaved by Golgi-resident proteases releasing the N-terminal product which traffics to the nucleus to effect transcriptional responses...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28374012/activation-of-ras-erk-signaling-and-gsk-3-by-amyloid-precursor-protein-and-amyloid-beta-facilitates-neurodegeneration-in-alzheimer-s-disease
#7
Lisa Kirouac, Alexander J Rajic, David H Cribbs, Jaya Padmanabhan
It is widely accepted that amyloid β (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to intracellular signaling events preceding AD pathogenesis. The data presented here demonstrate that APP expression and neuronal exposure to oligomeric Aβ42 enhance Ras/ERK signaling cascade and glycogen synthase kinase 3 (GSK-3) activation. We find that RNA interference (RNAi)-directed knockdown of APP in B103 rat neuroblastoma cells expressing APP inhibits Ras-ERK signaling and GSK-3 activation, indicating that APP acts upstream of these signal transduction events...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28359080/lithium-enhances-the-antitumour-effect-of-temozolomide-against-tp53-wild-type-glioblastoma-cells-via-nfat1-fasl-signalling
#8
Sheng Han, Lingxuan Meng, Yang Jiang, Wen Cheng, Xinxin Tie, Junzhe Xia, Anhua Wu
BACKGROUND: We previously showed that activation of the nuclear factor of activated T cells (NFAT)1/Fas ligand (FasL) pathway induces glioma cell death. Lithium (Li) is an inhibitor of glycogen synthase kinase (GSK)-3 that activates NFAT1/FasL signalling. Temozolomide (TMZ) inhibits GSK-3 and activates Fas in tumour protein (TP)53 wild-type (TP53wt) glioma cells. The present study investigated the combinational effects of TMZ and low-dose Li on TP53wt glioma cells. METHODS: The combined effect of TMZ and Li was examined in TP53wt U87 and primary glioma cells and a mouse xenograft model...
March 30, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28338397/clove-and-its-active-compound-attenuate-free-fatty-acid-mediated-insulin-resistance-in-skeletal-muscle-cells-and-in-mice
#9
Safina Ghaffar, Shabbir Khan Afridi, Meha Fatima Aftab, Munazza Murtaza, Rahman M Hafizur, Sara Sara, Sabira Begum, Rizwana Sanaullah Waraich
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation...
April 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28337318/development-of-18-f-maleimide-based-glycogen-synthase-kinase-3%C3%AE-ligands-for-positron-emission-tomography-imaging
#10
Kongzhen Hu, Debasis Patnaik, Thomas Lee Collier, Katarzyna N Lee, Han Gao, Matthew R Swoyer, Benjamin H Rotstein, Hema S Krishnan, Steven H Liang, Jin Wang, Zhiqiang Yan, Jacob M Hooker, Neil Vasdev, Stephen J Haggarty, Ming-Yu Ngai
Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme's aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28328738/inhibition-of-hippocampal-long-term-potentiation-by-high-fat-diets-is-it-related-to-an-effect-of-palmitic-acid-involving-glycogen-synthase-kinase-3
#11
Ana Contreras, Danila Del Rio, Ana Martínez, Carmen Gil, Lidia Morales, Mariano Ruiz-Gayo, Nuria Del Olmo
High-fat diets (HFD) impair hippocampal-dependent learning and memory and produce important changes in synaptic transmission by enhancing glutamate uptake, decreasing synaptic efficacy, and inhibiting plasticity mechanisms such as N-methyl-D-aspartate-mediated long-term depression (LTD) within the hippocampus. Adolescent animals seem to be particularly susceptible to the detrimental effect of HFD as dietary treatments carried out between weaning and early adulthood are much more efficient in terms of hippocampal damage that those carried out during the adult period...
April 12, 2017: Neuroreport
https://www.readbyqxmd.com/read/28324067/gestational-protein-restriction-impairs-glucose-disposal-in-the-gastrocnemius-muscles-of-female-rats
#12
Chellakkan S Blesson, Vijayakumar Chinnathambi, Sathish Kumar, Chandrasekhar Yallampalli
Gestational low-protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring, but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP-exposed female offspring. Pregnant rats were fed a control (20% protein) or an isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months, and gastrocnemius muscles were treated with insulin ex vivo for 30 minutes...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#13
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28299185/recent-advances-in-understanding-the-cellular-roles-of-gsk-3
#14
REVIEW
Kevin W Cormier, James R Woodgett
Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed protein kinase that sits at the nexus of multiple signaling pathways. Its deep integration into cellular control circuits is consummate to its implication in diseases ranging from mood disorders to diabetes to neurodegenerative diseases and cancers. The selectivity and insulation of such a promiscuous kinase from unwanted crosstalk between pathways, while orchestrating a multifaceted response to cellular stimuli, offer key insights into more general mechanisms of cell regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28288414/butyrate-induces-ros-mediated-apoptosis-by-modulating-mir-22-sirt-1-pathway-in-hepatic-cancer-cells
#15
Kishor Pant, Ajay K Yadav, Parul Gupta, Rakibul Islam, Anoop Saraya, Senthil K Venugopal
Butyrate is one of the short chain fatty acids, produced by the gut microbiota during anaerobic fermentation of dietary fibres. It has been shown that it can inhibit tumor progression via suppressing histone deacetylase and can induce apoptosis in cancer cells. However, the comprehensive pathway by which butyrate mediates apoptosis and growth arrest in cancer cells still remains unclear. In this study, the role of miR-22 in butyrate-mediated ROS release and induction of apoptosis was determined in hepatic cells...
March 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/28283665/il-18-dependent-nkg2d-ligand-upregulation-on-accessory-cells-is-mediated-by-the-pi3k-gsk-3-pathway
#16
Joshua D Brandstadter, Huiyao Chen, Songfu Jiang, Xiaopei Huang, Yiping Yang
NK cells are critical for the control of viral infections. Studies have shown that efficient NK cell activation in response to infection with VV in vivo requires multiple pathways, including the NKG2D pathway. We have recently shown that IL-18 is necessary for the activation of NK cells through upregulation of the NKG2D ligand Rae-1 on DCs upon VV infection. However, how IL-18R signaling on the accessory cells contributes to Rae-1 up-regulation remains to be defined. In this study, we found IL-18-mediated Rae-1 up-regulation in accessory cells, including macrophages and DCs, to be dependent on the MyD88-PI3K pathway...
March 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28281841/lncrna-nonratt021972-sirna-normalized-the-dysfunction-of-hepatic-glucokinase-through-akt-signaling-in-t2dm-rats
#17
Miaomiao Song, Lifang Zou, Lichao Peng, Shuangmei Liu, Bing Wu, Zhihua Yi, Yun Gao, Chunping Zhang, Hong Xu, Yurong Xu, Mengxia Tang, Shouyu Wang, Yun Xue, Tianyu Jia, Shanhong Zhao, Shangdong Liang, Guilin Li
Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3β. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases. AIMS: This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats...
March 10, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28272406/o-glcnacylation-of-skn-1-modulates-the-lifespan-and-oxidative-stress-resistance-in-caenorhabditis-elegans
#18
Hongyuan Li, Xin Liu, Dan Wang, Liangping Su, Tingting Zhao, Zhongwei Li, Cong Lin, Yu Zhang, Baiqu Huang, Jun Lu, Xiaoxue Li
In C. elegans, the transcription factor skinhead-1 (SKN-1), the ortholog of human NF-E2-related factor 2 (Nrf-2), plays important roles in oxidative stress defense and aging processes. It has been documented that the activity of SKN-1 is regulated by its phosphorylation modification. However, whether other posttranslational modifications of SKN-1 affect its function remains unclear to date. Here we report, for the first time, that SKN-1 is O-GlcNAcylated at Ser470 and Thr493 by O-GlcNActransferase OGT-1. By generating the double mutations of Ser470/Thr493 in the wild type and skn-1(zu67) worms, respectively, we found that disruption of O-GlcNAc modification on SKN-1 repressed the accumulation of SKN-1 in the intestinal nuclei, and decreased the activities of SKN-1 in modulating lifespan and oxidative stress resistance...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28256546/promoting-in-vivo-remyelination-with-small-molecules-a-neuroreparative-pharmacological-treatment-for-multiple-sclerosis
#19
Eva María Medina-Rodríguez, Ana Bribián, Amanda Boyd, Valle Palomo, Jesús Pastor, Alfonso Lagares, Carmen Gil, Ana Martínez, Anna Williams, Fernando de Castro
Multiple Sclerosis (MS) is a neurodegenerative disease where immune-driven demyelination occurs with inefficient remyelination, but therapies are limited, especially those to enhance repair. Here, we show that the dual phosphodiesterase (PDE)7- glycogen synthase kinase (GSK)3 inhibitor, VP3.15, a heterocyclic small molecule with good pharmacokinetic properties and safety profile, improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28253732/the-indirubin-derivative-6-bromoindirubin-3-oxime-6bio-activates-proteostatic-modules-reprograms-cellular-bioenergetics-pathways-and-exerts-anti-aging-effects
#20
Eleni Tsakiri, Nicolas Gaboriaud-Kolar, Kalliopi Iliaki, Job Tchoumtchoua, Eleni-Dimitra Papanagnou, Sofia Chatzigeorgiou, Konstantinos Tallas, Emmanuel Mikros, Maria Halabalaki, Alexios-Leandros Skaltsounis, Ioannis P Trougakos
AIMS: Organismal aging can be delayed by mutations that either activate stress responses or reduce the nutrients sensing pathways signaling; thus, by using Drosophila melanogaster as an in vivo experimental screening platform we searched for compounds that modulate these pathways. RESULTS: We noted that oral administration of the glycogen synthase kinase 3 (Gsk-3) inhibitor 6-bromoindirubin-3'-oxime (6BIO) in Drosophila flies extended healthy lifespan. 6BIO is not metabolized in flies' tissues; modulated bioenergetic pathways, decreased lipid and glucose tissues' load, activated antioxidant and proteostatic modules and enhanced resistance to stressors...
March 2, 2017: Antioxidants & Redox Signaling
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