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Lithium gsk3

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https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#1
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606794/antifibrotic-actions-of-peroxisome-proliferator-activated-receptor-%C3%AE-ligands-in-corneal-fibroblasts-are-mediated-by-%C3%AE-catenin-regulated-pathways
#2
Kye-Im Jeon, Richard P Phipps, Patricia J Sime, Krystel R Huxlin
Wound healing after corneal injury typically involves fibrosis, with transforming growth factor β1 (TGF-β1) as one of its strongest mediators. A class of small molecules-peroxisome proliferator-activated receptor γ (PPARγ) ligands-exert potent antifibrotic effects in the cornea by blocking phosphorylation of p38 mitogen-activated protein kinase (MAPK). However, why this blocks fibrosis remains unknown. Herein, we show that PPARγ ligands (rosiglitazone, troglitazone, and 15-deoxy-Δ12,14-prostaglandin J2) decrease levels of β-catenin...
June 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28566716/glycogen-synthase-kinase-3%C3%AE-inhibitors-prevent-hepatitis-c-virus-release-assembly-through-perturbation-of-lipid-metabolism
#3
Mohammed A Sarhan, Mohamed S Abdel-Hakeem, Andrew L Mason, D Lorne Tyrrell, Michael Houghton
Direct acting antivirals against hepatitis C virus (HCV) have markedly improved cure rates in the past few years. However, they are expensive, with only few targeting host cell factors, and affecting virus assembly and release. Huh7.5 cells infected with a JFH-1 clone of HCV were treated with two different glycogen synthase kinase (GSK3)-β inhibitors; AR-A014418 and lithium chloride. Intra- and extracellular HCV virions and specific infectivity was determined using real-time RT-PCR and TCID50, and changes in lipid production were identified by enzyme-linked immunoassay and mass spectrometry analyses...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28449557/wnt-and-gsk3-signaling-pathways-in-bipolar-disorder-clinical-and-therapeutic-implications
#4
REVIEW
Ather Muneer
The neurobiology of bipolar disorder, a chronic and systemic ailment is not completely understood. The bipolar phenotype manifests in myriad ways, and psychopharmacological agents like lithium have long term beneficial effects. The enzyme glycogen synthase kinase 3 (GSK3) has come into focus, as lithium and several other mood stabilizing medications inhibit its activity. This kinase and its key upstream modulator, Wnt are dysregulated in mood disorders and there is a growing impetus to delineate the chief substrates involved in the development of these illnesses...
May 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28363635/glycogen-synthase-kinase-3-gsk3-regulates-tnf-production-and-haemocyte-phagocytosis-in-the-immune-response-of-chinese-mitten-crab-eriocheir-sinensis
#5
Xiaowei Li, Zhihao Jia, Weilin Wang, Lingling Wang, Zhaoqun Liu, Bin Yang, Yunke Jia, Xiaorui Song, Qilin Yi, Limei Qiu, Linsheng Song
Glycogen synthase kinase-3 (GSK3) is a serine/threonine protein kinase firstly identified as a regulator of glycogen synthesis. Recently, it has been proved to be a key regulator of the immune reaction. In the present study, a GSK3 homolog gene (designated as EsGSK3) was cloned from Chinese mitten crab, Eriocheir sinensis. The open reading frame (ORF) was 1824 bp, which encoded a predicted polypeptide of 607 amino acids. There was a conserved Serine/Threonine Kinase domain and a DNA binding domain found in EsGSK3...
March 29, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28081383/inhibiting-effect-of-lithium-chloride-on-endotoxin-induced-uveitis-in-rats
#6
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/27752079/dixdc1-contributes-to-psychiatric-susceptibility-by-regulating-dendritic-spine-and-glutamatergic-synapse-density-via-gsk3-and-wnt-%C3%AE-catenin-signaling
#7
P-M Martin, R E Stanley, A P Ross, A E Freitas, C E Moyer, A C Brumback, J Iafrati, K S Stapornwongkul, S Dominguez, S Kivimäe, K A Mulligan, M Pirooznia, W R McCombie, J B Potash, P P Zandi, S M Purcell, S J Sanders, Y Zuo, V S Sohal, B N R Cheyette
Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls...
October 18, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27688851/anti-malarial-activities-of-two-soil-actinomycete-isolates-from-sabah-via-inhibition-of-glycogen-synthase-kinase-3%C3%AE
#8
Dhiana Efani Dahari, Raifana Mohamad Salleh, Fauze Mahmud, Lee Ping Chin, Noor Embi, Hasidah Mohd Sidek
Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection...
August 2016: Tropical Life Sciences Research
https://www.readbyqxmd.com/read/27630757/gsk3-signalling-and-redox-status-in-bipolar-disorder-evidence-from-lithium-efficacy
#9
REVIEW
Antonina Luca, Carmela Calandra, Maria Luca
Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27537208/up-regulation-of-the-large-conductance-ca2-activated-k-channel-by-glycogen-synthase-kinase-gsk3%C3%AE
#10
Myriam Fezai, Musaab Ahmed, Zohreh Hosseinzadeh, Florian Lang
BACKGROUND/AIMS: The pleotropic functions of the large conductance Ca2+-activated K+ channels (maxi K+ channel or BK channels) include regulation of neuronal excitation and cell volume. Kinases participating in those functions include the glycogen synthase kinase GSK3 ß which is under negative control of protein kinase B (PKB/Akt). GSK3ß is inhibited by the antidepressant Lithium. The present study thus explored whether GSK3ß modifies the activity of BK channels. METHODS: cRNA encoding the Ca2+ insensitive BK channel mutant BKM513I+Δ899-903 was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type GSK3ß, inactive K85RGSK3ß, or wild-type GSK3ß with wild-type PKB...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27525971/allostimulatory-effects-of-dendritic-cells-with-characteristic-features-of-a-regulatory-phenotype
#11
M Kouwenberg, C W M Jacobs, J van der Vlag, L B Hilbrands
INTRODUCTION: Tolerogenic dendritic cells (DCs) have the potential to prolong graft survival after transplantation. Tolerogenic DCs are in general characterized by a low expression of co-stimulatory molecule and a high IL-10:IL-12 production ratio. Based on promising results with earlier used alternatively activated DCs, we aimed to generate in culture potentially tolerogenic DC by simultaneously blocking GSK3 by lithium chloride (LiCl) and stimulating TLR2 by PAM3CysSerLys4. MATERIALS AND METHODS: Bone marrow-derived LiClPAM3 DCs were generated by the addition of LiCl 24 hours before harvesting, and one hour later PAM3CysSerLys4...
2016: PloS One
https://www.readbyqxmd.com/read/27490211/tideglusib-induces-apoptosis-in-human-neuroblastoma-imr32-cells-provoking-sub-g0-g1-accumulation-and-ros-generation
#12
Theodore Lemuel Mathuram, Vilwanathan Ravikumar, Lisa M Reece, Selvaraju Karthik, Changam Sheela Sasikumar, Kotturathu Mammen Cherian
Neuroblastoma is the most common tumor amongst children amounting to nearly 15% of cancer deaths. This cancer is peculiar in its characteristics, exhibiting differentiation, maturation and metastatic transformation leading to poor prognosis and low survival rates among children. Chemotherapy, though toxic to normal cells, has shown to improve the survival of the patient with emphasis given more towards targeting angiogenesis. Recently, Tideglusib was designed as an 'Orphan Drug' to target the neurodegenerative Alzheimer's disease and gained significant momentum in its function during clinical trials...
September 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27390215/antinociceptive-and-anti-inflammatory-effects-of-ketamine-and-the-relationship-to-its-antidepressant-action-and-gsk3-inhibition
#13
COMPARATIVE STUDY
Eduardo Mulato do Vale, Cecília Coelho Xavier, Brenda Gomes Nogueira, Bruna Caldas Campos, Pedro Everson Alexandre de Aquino, Roberta Oliveira da Costa, Luzia Kalyne Almeida Moreira Leal, Silvânia Maria Mendes de Vasconcelos, Kelly Rose Tavares Neves, Glauce Socorro de Barros Viana
Ketamine (KET), a NMDA antagonist, exerts an antidepressant effect at subanaesthetic doses and possesses analgesic and anti-inflammatory activities. We evaluated the involvement of KET antinociceptive and anti-inflammatory effects with its antidepressant action. Male Swiss mice were subjected to formalin, carrageenan-induced paw oedema and forced swimming tests, for assessing antinociceptive, anti-inflammatory and antidepressant effects. The treatment groups were as follows: control, KET (2, 5 and 10 mg/kg), lithium (LI: 5 mg/kg) and KET2 + LI5 combination...
December 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27208492/na-k-atpase-dysfunction-causes-cerebrovascular-endothelial-cell-degeneration-in-rat-prefrontal-cortex-slice-cultures
#14
Yuki Kurauchi, Akinori Hisatsune, Takahiro Seki, Hiroshi Katsuki
Cerebrovascular endothelial cell dysfunction resulting in imbalance of cerebral blood flow contributes to the onset of psychiatric disorders such as depression, schizophrenia and bipolar disorder. Although decrease in Na(+), K(+)-ATPase activity has been reported in the patients with schizophrenia and bipolar disorder, the contribution of Na(+), K(+)-ATPase to endothelial cell dysfunction remains poorly understood. Here, by using rat neonatal prefrontal cortex slice cultures, we demonstrated that pharmacological inhibition of Na(+), K(+)-ATPase by ouabain induced endothelial cell injury...
August 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27167678/deficiency-of-diacylglycerol-kinase-%C3%AE-induces-lithium-sensitive-mania-like-behavior
#15
Takeshi Isozaki, Suguru Komenoi, Qiang Lu, Takako Usuki, Shuntaro Tomokata, Daisuke Matsutomo, Hiromichi Sakai, Kana Bando, Hiroshi Kiyonari, Fumio Sakane
The η isozyme of diacylglycerol kinase (DGK) is highly expressed in the hippocampus and Purkinje cells in the central nervous system. Recently, several genome-wide association studies have implicated DGKη in the etiology of bipolar disorder (BPD). However, it is still unknown whether DGKη is indeed related to BPD. In this study, we generated DGKη-knockout (KO) mice and performed behavioral tests such as the open field test, the elevated plus maze test and tail suspension test using the KO mice to investigate the effects of DGKη deficits on psychomotor behavior...
August 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27161213/glycogen-synthase-kinase-3-modulates-hyperosmotic-induced-urea-transporter-a1-relocation-in-the-inner-medullary-collecting-duct-cells
#16
Yong-Xia Li, Yun Huang, Song Liu, Yan Mao, Cheng-Yan Yuan, Xiao Yang, Li-Jun Yao
AIM: Glycogen synthase kinase 3 (GSK3) regulates urine concentration by mediating the vasopressin-induced aquaporin 2 expression and water permeability, although it is unknown whether GSK3 also mediates the accumulation of the urea transporter A1 (UT-A1). The aim of this study is to investigate the effect of GSK3 on UT-A1 distribution. METHODS: Mouse inner medullary collecting duct 3 cells were transfected with UT-A1-GFP construct. The stable transfected cells were cultured under hypertonic conditions, treated with GSK3 inhibitor lithium chloride, GSK3 activator, lysosome or proteasome inhibitor...
2016: Nephron
https://www.readbyqxmd.com/read/27140617/pi3k-resistant-gsk3-controls-adiponectin-formation-and-protects-from-metabolic-syndrome
#17
Hong Chen, Abul Fajol, Miriam Hoene, Bingbing Zhang, Erwin D Schleicher, Yun Lin, Carsten Calaminus, Bernd J Pichler, Cora Weigert, Hans U Häring, Florian Lang, Michael Föller
Metabolic syndrome is characterized by insulin resistance, obesity, and dyslipidemia. It is the consequence of an imbalance between caloric intake and energy consumption. Adiponectin protects against metabolic syndrome. Insulin-induced signaling includes activation of PI3 kinase and protein kinase B (PKB)/Akt. PKB/Akt in turn inactivates glycogen synthase kinase (GSK) 3, a major regulator of metabolism. Here, we studied the significance of PI3K-dependent GSK3 inactivation for adiponectin formation in diet-induced metabolic syndrome...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27128528/inhibitors-of-glycogen-synthase-kinase-3-with-exquisite-kinome-wide-selectivity-and-their-functional-effects
#18
Florence F Wagner, Joshua A Bishop, Jennifer P Gale, Xi Shi, Michelle Walk, Joshua Ketterman, Debasis Patnaik, Doug Barker, Deepika Walpita, Arthur J Campbell, Shannon Nguyen, Michael Lewis, Linda Ross, Michel Weïwer, W Frank An, Andrew R Germain, Partha P Nag, Shailesh Metkar, Taner Kaya, Sivaraman Dandapani, David E Olson, Anne-Laure Barbe, Fanny Lazzaro, Joshua R Sacher, Jaime H Cheah, David Fei, Jose Perez, Benito Munoz, Michelle Palmer, Kimberly Stegmaier, Stuart L Schreiber, Edward Scolnick, Yan-Ling Zhang, Stephen J Haggarty, Edward B Holson, Jen Q Pan
The mood stabilizer lithium, the first-line treatment for bipolar disorder, is hypothesized to exert its effects through direct inhibition of glycogen synthase kinase 3 (GSK3) and indirectly by increasing GSK3's inhibitory serine phosphorylation. GSK3 comprises two highly similar paralogs, GSK3α and GSK3β, which are key regulatory kinases in the canonical Wnt pathway. GSK3 stands as a nodal target within this pathway and is an attractive therapeutic target for multiple indications. Despite being an active field of research for the past 20 years, many GSK3 inhibitors demonstrate either poor to moderate selectivity versus the broader human kinome or physicochemical properties unsuitable for use in in vitro systems or in vivo models...
July 15, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27126323/lithium-induced-neuroprotection-in-stroke-involves-increased-mir-124-expression-reduced-re1-silencing-transcription-factor-abundance-and-decreased-protein-deubiquitination-by-gsk3%C3%AE-inhibition-independent-pathways
#19
Thorsten R Doeppner, Britta Kaltwasser, Eduardo H Sanchez-Mendoza, Ahmet B Caglayan, Mathias Bähr, Dirk M Hermann
Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry...
March 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27122541/what-we-need-to-know-about-the-effect-of-lithium-on-the-kidney
#20
REVIEW
Rujun Gong, Pei Wang, Lance Dworkin
Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis, and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis...
December 1, 2016: American Journal of Physiology. Renal Physiology
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