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https://www.readbyqxmd.com/read/29332037/increased-vulnerability-of-the-hippocampus-in-transgenic-mice-overexpressing-app-and-triple-repeat-tau
#1
Andrew Arner, Edward Rockenstein, Michael Mante, Jazmin Florio, Deborah Masliah, Bahar Salehi, Anthony Adame, Cassia Overk, Eliezer Masliah, Robert A Rissman
 Alzheimer's disease (AD) is the most common tauopathy, characterized by progressive accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. While pathology associated with the 4-repeat (4R) tau isoform is more abundant in corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau isoforms accumulate in AD. Many studies have investigated interactions between Aβ and 4R tau in double transgenic mice, but few, if any, have examined the effects of Aβ with 3R tau. To examine this relationship, we crossed our APP751 mutant line with our recently characterized 3R tau mutant model to create a bigenic line (hAPP-3RTau) to model AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331582/inositol-polyphosphates-contribute-to-cellular-circadian-rhythms-implications-for-understanding-lithium-s-molecular-mechanism
#2
Heather Wei, Dominic Landgraf, George Wang, Michael J McCarthy
Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP6) has effects on circadian rhythms...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329030/pdok2-caspase-3-dependent-glioma-cell-growth-arrest-by-nitidine-chloride
#3
Ravindra Pramod Deshpande, Phanithi Prakash Babu
BACKGROUND: Nitidine chloride (NC) is known to exert anticancer and anti-metastatic effects on a variety of tumors. Recently, NC has also been shown to inhibit PIK3/AKT/mTOR axis in U87 human glioma cells. METHODS: The study shows NC employing pDok2, caspase 3 dependent cell death in C6 rat glioma and U87 human malignant glioblastoma cells. The effect of NC on glioblastoma cell lines was accessed by MTT, clonogenic and wound healing assays. Cell cycle analysis was performed by FACS...
July 29, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29328365/nuclear-gsk3%C3%AE-induces-dna-double-strand-break-repair-by-phosphorylating-53bp1-in-glioblastoma
#4
Yong Yang, Tiantian Lei, Suya Du, Rongsheng Tong, Hailian Wang, Jiao Yang, Juan Huang, Minghan Sun, Yi Wang, Zhi Dong
Glioblastoma is the most malignant and lethal subtype brain tumors with high risk of recurrence and therapeutic resistance. Emerging evidence has indicated that glycogen synthesis kinase 3 (GSK3)β plays oncogenic roles in multiple tumor types; however, the underlying mechanisms remain largely unknown. It has also been demonstrated that p53 binding protein 1 (53BP1) plays a central role in DNA double-strand break (DSB) repair. This study aimed to reveal the significance of GSK3β translocation from the cytoplasm to the nucleus, and to determine whether GSK3β induces DNA DSB repair in the nuclei of glioblastoma cells via phospho-53BP1...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29320691/network-features-and-dynamical-landscape-of-naive-and-primed-pluripotency
#5
Benjamin Pfeuty, Clémence Kress, Bertrand Pain
Although the broad and unique differentiation potential of pluripotent stem cells relies on a complex transcriptional network centered around Oct4, Sox2, and Nanog, two well-distinct pluripotent states, called "naive" and "primed", have been described in vitro and markedly differ in their developmental potential, their expression profiles, their signaling requirements, and their reciprocal conversion. Aiming to determine the key features that segregate and coordinate these two states, data-driven optimization of network models is performed to identify relevant parameter regimes and reduce network complexity to its core structure...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29316313/microrna-21-promotes-glioma-cell-proliferation-and-inhibits-senescence-and-apoptosis-by-targeting-spry1-via-the-pten-pi3k-akt-signaling-pathway
#6
Chang Chai, Lai-Jun Song, Shuang-Yin Han, Xi-Qing Li, Ming Li
AIMS: Our study aims to investigate the effect of microRNA-21 (miR-21) on the proliferation, senescence, and apoptosis of glioma cells by targeting SPRY1 via the PTEN/PI3K/AKT signaling pathway. METHODS: Glioma tissues and brain tissues were collected for this study after surgical decompression for traumatic brain injury. RT-qPCR was employed to measure mRNA levels of miR-21, SPRY1, PTEN, PI3K, and AKT, and Western blotting was conducted to determine protein levels of SPRY1, PTEN, PI3K, AKT, p-AKT, Caspase-3, Caspase-9, P53, GSK3, and p-GSK3...
January 5, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29305881/liver-carbohydrates-metabolism-a-new-islet-neogenesis-associated-protein-peptide-ingap-pp-target
#7
Hernán Gonzalo Villagarcía, Carolina Lisi Román, María Cecilia Castro, Luisa Arbeláez González, María Teresa Ronco, Daniel Eleazar Francés, María Laura Massa, Bárbara Maiztegui, Luis Emilio Flores, Juan José Gagliardino, Flavio Francini
Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3β (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined...
January 3, 2018: Peptides
https://www.readbyqxmd.com/read/29298515/vitex-rotundifolia-fruit-suppresses-the-proliferation-of-human-colorectal-cancer-cells-through-down-regulation-of-cyclin-d1-and-cdk4-via-proteasomal-dependent-degradation-and-transcriptional-inhibition
#8
Hun Min Song, Gwang Hun Park, Su Bin Park, Hyun-Seok Kim, Ho-Jun Son, Yurry Um, Jin Boo Jeong
Viticis Fructus (VF) as the dried fruit from Vitex rotundifolia L. used as a traditional medicine for treating inflammation, headache, migraine, chronic bronchitis, eye pain, and gastrointestinal infections has been reported to have antiproliferative effects against various cancer cells, including breast, lung and colorectal cancer cells. However, the molecular mechanisms by which VF mediates the inhibitory effect of the proliferation of cancer cells have not been elucidated in detail. In this study, we investigated the molecular mechanism of VF on the down-regulation of cyclin D1 and CDK4 level associated with cancer cell proliferation...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29247183/rab-gtpase-binding-effector-protein-2-rabep2-is-a-primed-substrate-for-glycogen-synthase-kinase-3-gsk3
#9
Lisa Logie, Lidy Van Aalten, Axel Knebel, Thomas Force, C James Hastie, Hilary MacLauchlan, David G Campbell, Robert Gourlay, Alan Prescott, Jane Davidson, Will Fuller, Calum Sutherland
Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29244860/lithium-reduces-blood-glucose-levels-but-aggravates-albuminuria-in-btbr-ob-ob-mice
#10
Theun de Groot, Lars Damen, Leanne Kosse, Mohammad Alsady, Rosalinda Doty, Ruben Baumgarten, Susan Sheehan, Johan van der Vlag, Ron Korstanje, Peter M T Deen
Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy...
2017: PloS One
https://www.readbyqxmd.com/read/29237029/organization-of-vascular-cells-in-the-haustorium-of-the-parasitic-flowering-plant-cuscuta-japonica
#11
Kohki Shimizu, Akitaka Hozumi, Koh Aoki
The stem parasite dodder, Cuscuta japonica, has evolved a specialized root-like organ, the haustorium, which is differentiated from stem. In order to uptake water and nutrients, C. japonica reprograms haustorial cells to vascular cells, connecting the host's vascular system to the parasite's. However, little is known about vascular differentiation in haustoria. In this study, we first confirmed the temporal and spatial expression profiles of vascular cell type-specific genes, CjAPL, CjSEOR1, CjWOX4, and CjTED7, to examine whether phloem companion cells, developing sieve elements, procambial cells, and differentiating xylem cells, respectively, are present in the haustoria...
December 11, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29234272/differential-roles-of-glycogen-synthase-kinase-3-subtypes-alpha-and-beta-in-cortical-development
#12
Yan-Xia Ma, Xiu-Li Wang, Jian-Quan Chen, Bin Li, Eun-Mi Hur, Saijilafu
Glycogen synthase kinases 3 (GSK3) α and β are expressed in the nervous system, and disruption of GSK3 signaling has been implicated in a wide range of neurodevelopmental and psychiatric disorders. Although several studies have established a role of GSK3 signaling in the nervous system, much less is known about isoform-specific functions. Here, we have examined the role of GSK3α and GSK3β in the developing neocortex by performing in utero electroporation with specific small interfering RNAs targeting each isoform...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29232553/synthetic-lethality-of-combined-bcl-2-inhibition-and-p53-activation-in-aml-mechanisms-and-superior-antileukemic-efficacy
#13
Rongqing Pan, Vivian Ruvolo, Hong Mu, Joel D Leverson, Gwen Nichols, John C Reed, Marina Konopleva, Michael Andreeff
Evasion of apoptosis is a hallmark of cancer. Bcl-2 and p53 represent two important nodes in apoptosis signaling pathways. We find that concomitant p53 activation and Bcl-2 inhibition overcome apoptosis resistance and markedly prolong survival in three mouse models of resistant acute myeloid leukemia (AML). Mechanistically, p53 activation negatively regulates the Ras/Raf/MEK/ERK pathway and activates GSK3 to modulate Mcl-1 phosphorylation and promote its degradation, thus overcoming AML resistance to Bcl-2 inhibition...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29218084/regulation-of-osteogenic-differentiation-by-dna-methylation-of-the-dishevelled-gene-in-bone-marrow-mesenchymal-stem-cells
#14
Xiaofeng Han, Xinfeng Li, Guibin Zhong, Zude Liu
Bone marrow mesenchymal stem cells (BMSCs) are stem cells with multidirectional differentiation potential, which can be used as seed cells to repair and reconstruct many types of tissues and organs following injury or disease. Osteogenic differentiation involves a variety of pathway and factors, including cytokines, growth factors, and hormones. In the present study, we investigated the potential role of Dishevelled in osteogenic differentiation of BMSCs in induction medium containing the methyltransferase inhibitor 5-aza-2'-deoxycytidine...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29212798/the-gsk3-kinase-inhibitor-lithium-produces-unexpected-hyperphosphorylation-of-%C3%AE-catenin-a-gsk3-substrate-in-human-glioblastoma-cells
#15
Ata Ur Rahman Mohammed Abdul, Bhagya De Silva, Ronald K Gary
Lithium salt is a classic glycogen synthase kinase 3 (GSK3) inhibitor. Beryllium is a structurally-related inhibitor that is more potent but relatively uncharacterized. This study examined the effects of these inhibitors on the phosphorylation of endogenous GSK3 substrates. In NIH-3T3 cells, both salts caused a decrease in phosphorylated glycogen synthase, as expected. GSK3 inhibitors produce enhanced phosphorylation of Ser9 of GSK3β via a positive feedback mechanism, and both salts elicited this enhancement...
December 6, 2017: Biology Open
https://www.readbyqxmd.com/read/29207259/a-chemical-genetic-approach-reveals-the-distinct-roles-of-gsk3%C3%AE-and-gsk3%C3%AE-in-regulating-embryonic-stem-cell-fate
#16
Xi Chen, Ruizhe Wang, Xu Liu, Yongming Wu, Tao Zhou, Yujia Yang, Andrew Perez, Ying-Chu Chen, Liang Hu, Jean Paul Chadarevian, Amir Assadieskandar, Chao Zhang, Qi-Long Ying
Glycogen synthase kinase 3 (GSK3) plays a central role in diverse cellular processes. GSK3 has two mammalian isozymes, GSK3α and GSK3β, whose functions remain ill-defined because of a lack of inhibitors that can distinguish between the two highly homologous isozymes. Here, we show that GSK3α and GSK3β can be selectively inhibited in mouse embryonic stem cells (ESCs) using a chemical-genetic approach. Selective inhibition of GSK3β is sufficient to maintain mouse ESC self-renewal, whereas GSK3α inhibition promotes mouse ESC differentiation toward neural lineages...
December 4, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29203592/correction-of-gsk3%C3%AE-at-young-age-prevents-muscle-pathology-in-mice-with-myotonic-dystrophy-type-1
#17
Christina Wei, Lauren Stock, Leila Valanejad, Zachary A Zalewski, Rebekah Karns, Jack Puymirat, David Nelson, David Witte, Jim Woodgett, Nikolai A Timchenko, Lubov Timchenko
Myotonic dystrophy type 1 (DM1) is a progressive neuromuscular disease caused by expanded CUG repeats, which misregulate RNA metabolism through several RNA-binding proteins, including CUG-binding protein/CUGBP1 elav-like factor 1 (CUGBP1/CELF1) and muscleblind 1 protein. Mutant CUG repeats elevate CUGBP1 and alter CUGBP1 activity via a glycogen synthase kinase 3β (GSK3β)-cyclin D3-cyclin D-dependent kinase 4 (CDK4) signaling pathway. Inhibition of GSK3β corrects abnormal activity of CUGBP1 in DM1 mice [human skeletal actin mRNA, containing long repeats (HSALR ) model]...
December 4, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29197866/proteomic-analysis-reveals-a-new-benefit-of-periodic-mechanical-stress-on-chondrocytes
#18
Zeng Li, Zhen Wang, Shun Xu, Wenwei Liang, Weimin Fan
BACKGROUND/AIMS: In recent years, a variety of studies have been performed to investigate the cellular responses of periodic mechanical stress. In our previous studies, we found that periodic mechanical stress can promote proliferation and matrix synthesis through the integrin beta 1-mediated ERK1/2 pathway, and we used proteomic analysis to detect quantitative changes in chondrocytes under periodic mechanical stress. Despite these results, the effects and mechanisms of periodic mechanical stress are still not fully understood, so in this study we extended our study using phosphoproteomic techniques...
December 4, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29180818/oct4-supports-extended-lif-independent-self-renewal-and-maintenance-of-transcriptional-and-epigenetic-networks-in-embryonic-stem-cells
#19
Runsheng He, Besa Xhabija, Batool Al-Qanber, Benjamin L Kidder
Embryonic stem (ES) cell pluripotency is governed by OCT4-centric transcriptional networks. Conventional ES cells can be derived and maintained in vitro with media containing the cytokine leukemia inhibitory factor (LIF), which propagates the pluripotent state by activating STAT3 signaling, and simultaneous inhibition of glycogen synthase kinase-3 (GSK3) and MAP kinase/ERK kinase signaling. However, it is unclear whether overexpression of OCT4 is sufficient to overcome LIF-dependence. Here, we show that inducible expression of OCT4 (iOCT4) supports long-term LIF-independent self-renewal of ES cells cultured in media containing fetal bovine serum (FBS) and a glycogen synthase kinase-3 (GSK3) inhibitor, and in serum-free media...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29161257/regulation-of-camp-and-gsk3-signaling-pathways-contributes-to-the-neuronal-conversion-of-glioma
#20
Jinsoo Oh, Yongbo Kim, Lihua Che, Jeong Beom Kim, Gyeong Eon Chang, Eunji Cheong, Seok-Gu Kang, Yoon Ha
Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator)...
2017: PloS One
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