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https://www.readbyqxmd.com/read/29679546/lithium-chloride-licl-induced-autophagy-and-downregulated-expression-of-transforming-growth-factor-%C3%AE-induced-protein-tgfbi-in-granular-corneal-dystrophy
#1
Danyao Nie, Yun Peng, Ming Li, Xinhua Liu, Meilan Zhu, Lin Ye
This study evaluated whether lithium chloride (LiCl) prevents cytoplasmic accumulation of mutant-transforming growth factor β-induced protein (Mut-TGFBI) in granular corneal dystrophy (GCD) via activation of the autophagy pathway. Levels of TGFBI and microtubule-associated protein 1A/1B-light chain 3 (LC3) in 3 GCD patients and healthy controls were analyzed by immunohistochemistry (IHC) staining and Western blot. Primary corneal fibroblasts were isolated and transfected with wild type or mutant type TGFBI over-expressed vectors, and then treated with LiCl and/or autophagy inhibitor 3-methyladenine (3-MA)...
April 18, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29677638/gestational-glucocorticoid-exposure-disrupts-glucose-homeostasis-that-is-accompanied-by-increased-endoglin-and-dpp-4-activity-instead-of-gsk-3-in-rats
#2
Olufunto O Badmus, Olugbenga S Michael, Saheed Rabiu, Lawrence A Olatunji
Gestational glucocorticoid (GC) treatment has been associated with cardiometabolic disorder (CMD) in offspring's in later life. Elevated dipeptidyl peptidase-4 (DPP-4) activity, endoglin and glycogen synthase kinase-3 (GSK-3) has also been implicated in the development of insulin resistance (IR) and/or vascular inflammation. We aimed to investigate the impact of GC exposure on glucose metabolism and the circulating levels of inflammatory biomarkers, DPP-4 activity and GSK-3 in pregnant rats. Pregnant Wistar rats received either vehicle or dexamethasone (DEX; 0...
April 13, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29675957/endoplasmic-reticulum-stress-induces-spatial-memory-deficits-by-activating-gsk-3
#3
Li Lin, Jie Cao, Shu-Sheng Yang, Zheng-Qi Fu, Peng Zeng, Jiang Chu, Lin-Na Ning, Teng Zhang, Yan Shi, Qing Tian, Xin-Wen Zhou, Jian-Zhi Wang
Endoplasmic reticulum (ER) stress is involved in Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we injected tunicamycin (TM), a recognized ER stress inducer, into the brain ventricle of Sprague-Dawley (SD) rats to induce the unfolded protein response (UPR), demonstrated by the enhanced phosphorylation of pancreatic ER kinase (PERK), inositol-requiring enzyme-1 (IRE-1) and activating transcription factor-6 (ATF-6). We observed that UPR induced spatial memory deficits and impairments of synaptic plasticity in the rats...
April 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29661219/modulation-of-gsk-3-provides-cellular-and-functional-neuroprotection-in-the-rd10-mouse-model-of-retinitis-pigmentosa
#4
Alonso Sánchez-Cruz, Beatriz Villarejo-Zori, Miguel Marchena, Josefa Zaldivar-Díez, Valle Palomo, Carmen Gil, Ignacio Lizasoain, Pedro de la Villa, Ana Martínez, Enrique J de la Rosa, Catalina Hernández-Sánchez
BACKGROUND: Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death of photoreceptor cells, resulting in visual loss and, eventually, blindness. To date, no effective therapies have been transferred to clinic. Given the diverse genetic etiology of RP, targeting common cellular and molecular retinal alterations has emerged as a potential therapeutic strategy. METHODS: Using the Pde6b rd10/rd10 mouse model of RP, we investigated the effects of daily intraperitoneal administration of VP3...
April 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29571966/effects-of-the-antipsychotics-haloperidol-clozapine-and-aripiprazole-on-the-dendritic-spine
#5
Manabu Takaki, Masafumi Kodama, Yutaka Mizuki, Hiroki Kawai, Bunta Yoshimura, Makiko Kishimoto, Shinji Sakamoto, Yuko Okahisa, Norihito Yamada
Three types of antipsychotics, typical (e.g. haloperidol), atypical (e.g. clozapine), and dopamine partial agonist (e.g. aripiprazole), are administered for treatment of schizophrenia. These antipsychotics have different efficacy and side-effect profiles. We investigated whether aripiprazole, clozapine, and haloperidol differentially regulate the dendritic spine through the AKT-GSK-3 beta cascade. Dissociated cortical neurons from Sprague-Dawley rats were prepared and cultured for 28 days. Aripiprazole, clozapine, or haloperidol was administered to the rat cortical neurons...
March 20, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29545927/cdgap-arhgap31-is-regulated-by-rsk-phosphorylation-and-binding-to-14-3-3%C3%AE-adaptor-protein
#6
Ali Ben Djoudi Ouadda, Yi He, Viviane Calabrese, Hidetaka Ishii, Rony Chidiac, Jean-Philippe Gratton, Philippe P Roux, Nathalie Lamarche-Vane
Cdc42 GTPase-activating protein (CdGAP, also named ARHGAP31) is a negative regulator of the GTPases Rac1 and Cdc42. Associated with the rare developmental disorder Adams-Oliver Syndrome (AOS), CdGAP is critical for embryonic vascular development and VEGF-mediated angiogenesis. Moreover, CdGAP is an essential component in the synergistic interaction between TGFβ and ErbB-2 signaling pathways during breast cancer cell migration and invasion, and is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer...
February 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29532791/mechanisms-of-ketamine-action-as-an-antidepressant
#7
P Zanos, T D Gould
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects...
March 13, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29515772/the-c-raf-modulator-rrd-251-enhances-nuclear-c-raf-gsk-3-vdr-axis-signaling-and-augments-1-25-dihydroxyvitamin-d3-induced-differentiation-of-hl-60-myeloblastic-leukemia-cells
#8
Harrison T Supnick, Rodica P Bunaciu, Andrew Yen
Differentiation therapy is used in cancer treatment. Epidemiologic studies showed that higher vitamin D levels are associated with reduced cancer risks. However, the therapeutic doses needed for differentiation are accompanied by hypercalcemia and intolerable pathological sequelae. In the present work we evaluated if RRD-251, a small-molecule, can enhance vitamin D3-induced differentiation of leukemic cells, in the hope of decreasing the needed vitamin D3-dose. We demonstrate that RRD-251 enhances vitamin D3-induced differentiation of leukemic cells, the enrichment of the c-Raf kinase in the nucleus, the binding of nuclear c-Raf to GSK-3, increased phosphorylation of GSK-3 ser 21/9 inhibitory sites, and the binding of GSK-3 to VDR, where GSK-3 inhibition is known to enhance transcriptional activation by VDR...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29511646/treadmill-exercise-activates-pi3k-akt-signaling-pathway-leading-to-gsk-3%C3%AE-inhibition-in-the-social-isolated-rat-pups
#9
Lin Ru Wang, Seung-Soo Baek
Social isolation is known to precipitate depression-like symptoms in rodents and has emerged as a dependable paradigm to screen the behavioral and neurobiological changes observed in humans. In the present study, the undying mechanisms of treadmill exercise on social isolation-induced depression was evaluated. The rat pups in the social isolation groups were housed individually. The social isolation procedures started on the postnatal day 14. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34...
February 2018: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/29472293/degradation-of-the-endoplasmic-reticulum-anchored-transcription-factor-myrf-by-the-ubiquitin-ligase-scf-fbxw7-in-a-manner-dependent-on-the-kinase-gsk-3
#10
Shogo Nakayama, Kanae Yumimoto, Atsuki Kawamura, Keiichi I Nakayama
The ubiquitin-proteasome system regulates the abundance of many cellular proteins by mediating their targeted degradation. We previously developed a method-differential proteomics-based identification of ubiquitylation substrates (DiPIUS)-for the comprehensive identification of substrates for a given F-box protein subunit of SCF-type ubiquitin ligases. We have now applied DiPIUS to the F-box protein Fbxw7 in three cell lines (mHepa, Neuro2A, and C2C12) and thereby identified myelin regulatory factor (MyRF)-an endoplasmic reticulum-anchored transcription factor that is essential for myelination of nerves in the central nervous system-as a candidate substrate of Fbxw7 specifically in mHepa cells...
February 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29435775/quercetin-prevents-in-vivo-and-in-vitro-myocardial-hypertrophy-through-the-proteasome-gsk-3-pathway
#11
Kuixiang Chen, Mubarak Rekep, Wei Wei, Qian Wu, Qin Xue, Sujuan Li, Jiahui Tian, Quan Yi, Genshui Zhang, Guiping Zhang, Qing Xiao, Jiandong Luo, Yinghua Liu
PURPOSE: Quercetin, a flavonoid, has been reported to ameliorate cardiovascular diseases, such as cardiac hypertrophy. However, the mechanism is not completely understood. In this study, a mechanism related to proteasome-glycogen synthesis kinase 3 (GSK-3) was elucidated in rats and primary neonatal cardiomyocytes. METHODS: Rats were subjected to sham or constriction of abdominal aorta surgery groups and treated with or without quercetin for 8 weeks. Angiotensin II (Ang II)-induced primary cardiomyocytes were cultured with quercetin treatment or not for 48 h...
February 12, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29433844/glycogen-synthase-kinase-3%C3%AE-activity-and-cognitive-functioning-in-patients-with-bipolar-i-disorder
#12
Klaus Munkholm, Kamilla Woznica Miskowiak, Anne Sophie Jacoby, Maj Vinberg, Leda Leme Talib, Wagner Farid Gattaz, Lars Vedel Kessing
Cognitive deficits are common in patients with bipolar disorder (BD) in remission and may be associated with glycogen synthase kinase-3 (GSK-3) activity, which is inhibited by lithium. GSK-3 may be a relevant treatment target for interventions tailored at cognitive disturbances in BD but the relation between GSK-3 activity, cognition and lithium treatment is unknown. We therefore investigated the possible association between GSK-3 activity and cognition and whether lithium treatment moderates this association in patients with BD...
February 9, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29400073/oral-hormonal-therapy-with-ethinylestradiol-levonorgestrel-improves-insulin-resistance-obesity-and-glycogen-synthase-kinase-3-independent-of-circulating-mineralocorticoid-in-estrogen-deficient-rats
#13
Oluwaseun Aremu Adeyanju, Olaniyi Soetan, Ayodele Soladoye, Lawrence A Aderemi Olatunji
Estrogen deficiency has been associated with increased cardiovascular diseases (CVD) and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen-progestin therapy has been used as exogenous estrogen to normalise depressed estrogen level during menopause. Ovariectomized rodents mimic estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR).We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol/levonorgestrel (EEL) improves IR, obesity and glycogen synthase kinase-3 (GSK-3) through reduction in circulating mineralocorticoid level in ovariectomized rats...
February 3, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29396901/fine-tuning-of-canonical-wnt-stimulation-enhances-differentiation-of-pluripotent-stem-cells-independent-of-%C3%AE-catenin-mediated-t-cell-factor-signaling
#14
Joseph Chen, Christian M Nefzger, Fernando J Rossello, Yu B Y Sun, Sue Mei Lim, Xiaodong Liu, Suzan de Boer, Anja S Knaupp, Jinhua Li, Kathryn C Davidson, Jose M Polo, Tiziano Barberi
The canonical Wnt/β-catenin pathway is crucial for early embryonic patterning, tissue homeostasis, and regeneration. While canonical Wnt/β-catenin stimulation has been used extensively to modulate pluripotency and differentiation of pluripotent stem cells (PSCs), the mechanism of these two seemingly opposing roles has not been fully characterized and is currently largely attributed to activation of nuclear Wnt target genes. Here, we show that low levels of Wnt stimulation via ectopic expression of Wnt1 or administration of glycogen synthase kinase-3 inhibitor CHIR99021 significantly increases PSC differentiation into neurons, cardiomyocytes and early endodermal intermediates...
February 2, 2018: Stem Cells
https://www.readbyqxmd.com/read/29388174/gsk-3-inhibitors-a-double-edged-sword-an-update-on-tideglusib
#15
Theodore Lemuel Mathuram, Lisa M Reece, Kotturathu Mammen Cherian
GSK-3 inhibitors are an emerging tool for clinical interventions in human diseases and represent a niche area in combinational therapy. They possess diverse facets in applications of nervous system disorders, Type 2 diabetes, regenerative medicine and cancer. However, conflicting reports suggest the controversial role of GSK-3 inhibitors in cancers. This review aims to highlight the rise of GSK-3 inhibitors as tools for molecular-targeted research and its shift to a promising drug candidate. The review also focuses on key GSK-3 inhibitors and their roles in cancer and regenerative medicine with special emphasis to tideglusib...
January 31, 2018: Drug Research
https://www.readbyqxmd.com/read/29382566/overexpression-of-the-14-3-3%C3%AE-protein-in-uterine-leiomyoma-cells-results-in-growth-retardation-and-increased-apoptosis
#16
Qi Shen, Xiaoli Hu, Lulu Zhou, Shuangwei Zou, Lu-Zhe Sun, Xueqiong Zhu
Protein 14-3-3γ was significantly reduced in human uterine leiomyoma compared to the adjacent normal myometrium tissue. To investigate the possible link between the reduced 14-3-3γ expression and uterine leiomyoma growth, we have overexpressed 14-3-3γ protein in uterine leiomyomal cells and its effects on cell proliferation and apoptosis were analyzed. Over-expression of 14-3-3γ was achieved by transducing into two types of uterine leiomyoma cells (primary culture cells and immortal stem cells) with a 14-3-3γ expressing adenovirus vector...
January 27, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29335245/cdk9-mediated-phosphorylation-controls-the-interaction-of-tip60-with-the-transcriptional-machinery
#17
Prisca Brauns-Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer, Ulrich Maurer
The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60S90A , exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected...
February 2018: EMBO Reports
https://www.readbyqxmd.com/read/29334667/lithium-a-classic-drug-in-psychiatry-improves-nilotinib-mediated-antileukemic-effects
#18
Janaína Peixoto-da-Silva, Andrana K Calgarotto, Katiucha R Rocha, Caroline Palmeira-Dos-Santos, Soraya S Smaili, Gustavo J S Pereira, Fernando V Pericole, Adriana da Silva S Duarte, Sara T O Saad, Claudia Bincoletto
Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3β phosphorylation and Bcr-Abl oncoprotein levels reduction...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29310812/pgbr-extract-ameliorates-tnf-%C3%AE-induced-insulin-resistance-in-hepatocytes
#19
Fu-Chih Chen, Kuo-Ping Shen, Jin-Bor Chen, Hui-Li Lin, Chi-Long Hao, Hsueh-Wei Yen, Shyh-Yu Shaw
Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell...
January 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29306837/glycogen-synthase-kinase-3-and-its-inhibitors-potential-target-for-various-therapeutic-conditions
#20
REVIEW
A Prasanth Saraswati, S M Ali Hussaini, Namballa Hari Krishna, Bathini Nagendra Babu, Ahmed Kamal
Glycogen Synthase Kinase-3 (GSK-3) is a serine/threonine kinase which is ubiquitously expressed and is regarded as a regulator for various cellular events and signalling pathways. It exists in two isoforms, GSK-3α and GSK-3β and can phosphorylate a wide range of substrates. Aberrancy in the GSK-3 activity can lead to various diseases like Alzheimer's, diabetes, cancer, neurodegeneration etc., rendering it an attractive target to develop potent and specific inhibitors. The present review focuses on the recent developments in the area of GSK-3 inhibitors and also enlightens its therapeutic applicability in various disease conditions...
January 20, 2018: European Journal of Medicinal Chemistry
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