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https://www.readbyqxmd.com/read/27935293/redox-switch-for-the-inhibited-state-of-yeast-glycogen-synthase-mimics-regulation-by-phosphorylation
#1
Krishna Kishore Mahalingan, Sulochanadevi Baskaran, Anna A Depaoli-Roach, Peter J Roach, Thomas D Hurley
Glycogen synthase (GS) is the rate limiting enzyme in the synthesis of glycogen. Eukaryotic GS is negatively regulated by covalent phosphorylation and allosterically activated by glucose-6-phosphate (G6P). To gain structural insights into the inhibited state of the enzyme, we solved the crystal structure of yGsy2-R589A/R592A to a maximum resolution of 3.3 Å. The double mutant has an activity ratio similar to the phosphorylated enzyme and also retains the ability to be activated by G6P. When compared to the 2...
December 9, 2016: Biochemistry
https://www.readbyqxmd.com/read/27935243/mocdc14-is-important-for-septation-during-conidiation-and-appressorium-formation-in-magnaporthe-oryzae
#2
Chaohui Li, Shulin Cao, Chengkang Zhang, Yonghui Zhang, Qiang Zhang, Jin-Rong Xu, Chenfang Wang
As a typical foliar pathogen, appressorium formation and penetration are critical steps in the infection cycle of Magnaporthe oryzae. Because appressorium formation and penetration are closely co-regulated with cell cycle and Cdc14 phosphatases have antagonistic relationship with CDKs on proteins related to mitotic exits and cytokinesis, in this study we functionally characterized the MoCDC14 gene in M. oryzae. The Mocdc14 deletion mutant was significantly reduced in growth rate and conidiation. It also was defective in septum formation and nuclear distribution...
December 9, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/27933142/salidroside-reduces-tau-hyperphosphorylation-via-up-regulating-gsk-3%C3%AE-phosphorylation-in-a-tau-transgenic-drosophila-model-of-alzheimer-s-disease
#3
Bei Zhang, Qiongqiong Li, Xingkun Chu, Suya Sun, Shengdi Chen
BACKGROUND: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of Rhodiola rosea L., which has several pharmacological activities. The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27932674/metabolic-adaptations-in-skeletal-muscle-after-84-days-bed-rest-with-and-without-concurrent-flywheel-resistance-exercise
#4
José Maria Irimia, Mario Guerrero, Paula Rodriguez-Miguelez, Joan Aureli Cadefau, Per A Tesch, Roser Cussó, Rodrigo Fernandez-Gonzalo
As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n=9) or without (BR; n=12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1) and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α) and myostatin, were analysed in samples from m...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27931223/pattern-and-prognostic-value-of-cardiac-involvement-in-patients-with-late-onset-pompe-disease-a-comprehensive-cardiovascular-magnetic-resonance-approach
#5
Matthias Boentert, Anca Florian, Bianca Dräger, Peter Young, Ali Yilmaz
BACKGROUND: Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal α-1,4-glucosidase leading to accumulation of glycogen in target tissues with progressive organ failure. While the early infantile-onset form is characterized by early severe hypertrophic cardiomyopathy with cardiac and respiratory failure, clinically relevant cardiomyopathy seems to be uncommon in patients with late-onset Pompe disease, and the prevalence and nature of myocardial abnormalities are still to be clarified...
December 7, 2016: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/27929056/gsk-3%C3%AE-controls-nf-kappab-activity-via-ikk%C3%AE-nemo
#6
Senad Medunjanin, Lisa Schleithoff, Christian Fiegehenn, Soenke Weinert, Werner Zuschratter, Ruediger C Braun-Dullaeus
The NF-κB signaling pathway is central for the innate immune response and its deregulation is found in multiple disorders such as autoimmune, chronic inflammatory and metabolic diseases. IKKγ/NEMO is essential for NF-κB activation and NEMO dysfunction in humans has been linked to so-called progeria syndromes, which are characterized by advanced ageing due to age-dependent inflammatory diseases. It has been suggested that glycogen synthase kinase-3β (GSK-3β) participates in NF-κB regulation but the exact mechanism remained incompletely understood...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928614/moderate-exercise-ameliorates-dysregulated-hippocampal-glycometabolism-and-memory-function-in-a-rat-model-of-type-2-diabetes
#7
Takeru Shima, Takashi Matsui, Subrina Jesmin, Masahiro Okamoto, Mariko Soya, Koshiro Inoue, Yu-Fan Liu, Ignacio Torres-Aleman, Bruce S McEwen, Hideaki Soya
AIMS/HYPOTHESIS: Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals...
December 8, 2016: Diabetologia
https://www.readbyqxmd.com/read/27927596/quantification-of-muscle-pathology-in-infantile-pompe-disease
#8
Anne Schänzer, Ann-Kathrin Kaiser, Christian Mühlfeld, Martin Kulessa, Werner Paulus, Harald von Plein, Marianne Rohrbach, Lara Viergutz, Eugen Mengel, Thorsten Marquardt, Bern Neubauer, Till Acker, Andreas Hahn
The effects of enzyme replacement therapy (ERT) in infantile Pompe disease are variable, necessitating the identification of biomarkers to assess the severity of disease and response to ERT. The aims of this study were to investigate whether quantification of muscle pathology in infantile Pompe disease prior to and during ERT is feasible at the light microscope, and to develop a score that summarizes the degree of muscle pathology in a comprehensive manner from PAS-stained resin sections alone. We, therefore, determined glycogen load, extent of muscle fibre disruption, and amount of autophagic vacuoles in resin-embedded muscle biopsy specimens from 11 infantile Pompe patients and 2 with early childhood phenotype by quantitative methods, correlated the findings with ultrastructural analyses, compared PAS-stained resin sections with conventional PAS-stained cryosections, and related the quantified degree of muscle damage from infantile patients to the effects of ERT...
November 3, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27925497/anti-inflammatory-and-anticancer-effects-of-flavonol-glycosides-from-diplotaxis-harra-through-gsk3%C3%AE-regulation-in-intestinal-cells
#9
Imen Nasri, Rachid Chawech, Cynthia Girardi, Emmanuel Mas, Audrey Ferrand, Nathalie Vergnolle, Nicolas Fabre, Raoudha Mezghani-Jarraya, Claire Racaud-Sultan
CONTEXT AND OBJECTIVE: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 β (GSK3β) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3β and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3β. MATERIALS AND METHODS: Methanol extracts from D...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27924507/tppu-protects-tau-from-h2o2-induced-hyperphosphorylation-in-hek293-tau-cells-by-regulating-pi3k-akt-gsk-3%C3%AE-pathway
#10
En-Sheng Yao, Yan Tang, Xing-Hua Liu, Ming-Huan Wang
Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27923067/chronological-lifespan-in-yeast-is-dependent-on-the-accumulation-of-storage-carbohydrates-mediated-by-yak1-mck1-and-rim15-kinases
#11
Lu Cao, Yingzhi Tang, Zhenzhen Quan, Zhe Zhang, Stephen G Oliver, Nianshu Zhang
Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922641/ip3-accumulation-and-or-inositol-depletion-two-downstream-lithium-s-effects-that-may-mediate-its-behavioral-and-cellular-changes
#12
Y Sade, L Toker, N Z Kara, H Einat, S Rapoport, D Moechars, G T Berry, Y Bersudsky, G Agam
Lithium is the prototype mood stabilizer but its mechanism is still unresolved. Two hypotheses dominate-the consequences of lithium's inhibition of inositol monophosphatase at therapeutically relevant concentrations (the 'inositol depletion' hypothesis), and of glycogen-synthase kinase-3. To further elaborate the inositol depletion hypothesis that did not decisively determine whether inositol depletion per se, or phosphoinositols accumulation induces the beneficial effects, we utilized knockout mice of either of two inositol metabolism-related genes-IMPA1 or SMIT1, both mimic several lithium's behavioral and biochemical effects...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922496/metabolic-myopathies
#13
Mark A Tarnopolsky
PURPOSE OF REVIEW: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. RECENT FINDINGS: The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922231/evaluation-of-central-nervous-system-in-patients-with-glycogen-storage-disease-type-1a
#14
Yusuf Aydemir, Figen Gürakan, İnci Nur Saltık Temizel, Hülya Demir, Kader Karlı Oğuz, Dilek Yalnızoğlu, Meral Topçu, Hasan Özen, Aysel Yüce
We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group...
2016: Turkish Journal of Pediatrics
https://www.readbyqxmd.com/read/27922190/clc-3-promotes-osteogenic-differentiation-in-mc3t3-e1-cell-after-dynamic-compression
#15
Dawei Wang, Hao Wang, Feng Gao, Kun Wang, Fusheng Dong
ClC-3 chloride channel has been proved to have a relationship with the expression of osteogenic markers during osteogenesis, persistent static compression can upregulate the expression of ClC-3 and regulate osteodifferentiation in osteoblasts. However, there was no study about the relationship between the expression of ClC-3 and osteodifferentiation after dynamic compression. In this study, we applied dynamic compression on MC3T3-E1 cells to detect the expression of ClC-3, runt-related transcription factor 2 (Runx2), bone morphogenic protein-2 (BMP-2), osteopontin (OPN), nuclear-associated antigen Ki67 (Ki67) and proliferating cell nuclear antigen (PCNA) in biopress system, then we investigated the expression of these genes after dynamic compression with Chlorotoxin (specific ClC-3 chloride channel inhibitor) added...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27921399/antioxidant-and-antidiabetic-properties-of-tartary-buckwheat-rice-flavonoids-after-in-vitro-digestion
#16
Tao Bao, Ye Wang, Yu-Ting Li, Vemana Gowd, Xin-He Niu, Hai-Ying Yang, Li-Shui Chen, Wei Chen, Chong-de Sun
Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27919820/tnf-%C3%AE-and-cancer-cachexia-molecular-insights-and-clinical-implications
#17
REVIEW
Hetal J Patel, Bhoomika M Patel
Cancer cachexia characterized by a chronic wasting syndrome, involves skeletal muscle loss and adipose tissue loss and resistance to conventional nutritional support. Cachexia is responsible for the reduction in quality and length of life of cancer patients. It also decreases the muscle strength of the patients. The pro-inflammatory and pro-cachectic factors produced by the tumor cells have important role in genesis of cachexia. A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer...
December 2, 2016: Life Sciences
https://www.readbyqxmd.com/read/27918305/tuberous-sclerosis-complex-inactivation-disrupts-melanogenesis-via-mtorc1-activation
#18
Juxiang Cao, Magdalena E Tyburczy, Joel Moss, Thomas N Darling, Hans R Widlund, David J Kwiatkowski
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1). Patients with TSC develop hypomelanotic macules (white spots), but the molecular mechanisms underlying their formation are not fully characterized. Using human primary melanocytes and a highly pigmented melanoma cell line, we demonstrate that reduced expression of either TSC1 or TSC2 causes reduced pigmentation through mTORC1 activation, which results in hyperactivation of glycogen synthase kinase 3β (GSK3β), followed by phosphorylation of and loss of β-catenin from the nucleus, thereby reducing expression of microphthalmia-associated transcription factor (MITF), and subsequent reductions in tyrosinase and other genes required for melanogenesis...
December 5, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27918086/combined-therapy-with-swimming-exercise-and-a-diet-supplemented-with-diphenyl-diselenide-is-effective-against-age-related-changes-in-the-hepatic-metabolism-of-rats
#19
Suélen O Heck, Bruna C W Fulco, Caroline B Quines, Carla E S Oliveira, Marlon R Leite, José L Cechella, Cristina W Nogueira
Aging is characterized by a widespread loss of homeostasis in biological systems and is accompanied by pathophysiological changes including the liver injury. The aim of the present study was to investigate the effects of the combined therapy with swimming exercise (20 min session, five days/week during four weeks) and a diet supplemented with 1 ppm of (PhSe)2 on the hepatic metabolic alterations caused by aging in rats. In this study, male old Wistar rats had an increase in the epididymal fat relative weight, disturbances in the activities of hepatic enzymes associated to the glucose homeostasis, higher hepatic triglyceride content and higher activity of the plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27917273/involvement-of-microrna-133-and-29-in-cardiac-disturbances-in-diabetic-ovariectomized-rats
#20
Parisa Habibi, Alireza Alihemmati, Mohammadreza Nasirzadeh, Hadi Yousefi, Mohammadrasoul Habibi, Nasser Ahmadiasl
OBJECTIVES: Menopause and diabetes obviously increase the risk of cardiovascular disease in women. The aims of the present study were to evaluate the effects of ovariectomy in type 2 diabetes on the histology and expression of miRNA-29, miRNA-133, IGF-1 and Bcl-2 genes and Bcl-2 protein and caspase 3 activity in the hearts of female rats. MATERIALS AND METHODS: Forty Female Wistar rats were divided into four groups: control, sham, ovariectomized (OVX), and ovariectomized with type 2 diabetes (OVX...
November 2016: Iranian Journal of Basic Medical Sciences
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