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https://www.readbyqxmd.com/read/28432776/exploring-non-obvious-hydrophobic-binding-pockets-on-protein-surfaces-increasing-affinities-in-peptide-protein-interactions
#1
Lars Baltzer, Aleksandra Balliu
A 42-residue polypeptide conjugated to a small organic molecule capable of targeting the phosphorylated side chain of Ser-15 was shown to bind glycogen phosphorylase a (GPa) with a KD of 280 nM. The replacement of hydrophobic amino acids by Ala reduced affinities, whereas the incorporation of L-2-aminooctanoic acid (Aoc) increased affinities. Replacing Nle-5, Ile-9 and Leu-12 by Aoc reduced the KD from 280 nM to 27 nM. Downsizing the 42-mer to an 11-mer gave rise to an order of magnitude lower affinity for GPa but the 11-mer where Nle-5, Ile-9 and Leu-12 were replaced by Aoc showed a KD of 550 nM, comparable to that of the parent 42-mer...
April 22, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28432118/molecular-basis-for-exercise-induced-fatigue-the-importance-of-strictly-controlled-cellular-ca-2-handling
#2
Arthur J Cheng, Nicolas Place, Håkan Westerblad
The contractile function of skeletal muscle declines during intense or prolonged physical exercise, that is, fatigue develops. Skeletal muscle fibers fatigue acutely during highly intense exercise when they have to rely on anaerobic metabolism. Early stages of fatigue involve impaired myofibrillar function, whereas decreased Ca(2+) release from the sarcoplasmic reticulum (SR) becomes more important in later stages. SR Ca(2+) release can also become reduced with more prolonged, lower intensity exercise, and it is then related to glycogen depletion...
April 21, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28431381/zeaxanthin-ameliorates-high-glucose-induced-mesangial-cell-apoptosis-through-inhibiting-oxidative-stress-via-activating-akt-signalling-pathway
#3
Changjiang Ying, Lei Chen, Shanshan Wang, Yizhen Mao, Hongwei Ling, Wei Li, Xiaoyan Zhou
Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect...
April 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28429187/curcumin-reverses-the-depressive-like-behavior-and-insulin-resistance-induced-by-chronic-mild-stress
#4
Ji-Duo Shen, Yu Wei, Yu-Jie Li, Jing-Yi Qiao, Yu-Cheng Li
Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity...
April 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28428689/experimental-validation-of-antidiabetic-potential-of-cayratia-trifolia-l-domin-an-indigenous-medicinal-plant
#5
Shahid Iqbal Mohammed, Narendra Subhash Salunkhe, Kishor Sukhlal Vishwakarma, Vijay Laxminarayan Maheshwari
The present study was undertaken to evaluate antidiabetic and antioxidant activities of Cayratia trifolia root extract against streptozotocin induced diabetes in experimental rats to scientifically validate its use against diabetes in some parts of India. Ethanolic extract, showing the highest activity in in vitro experiments, was prepared in saline and administered orally to streptozotocin induced albino Wistar diabetic rats for 21 days. Biochemical parameters liver and muscles glycogen and in vivo antioxidant activity in normal, diabetic control, standard (metformin) and treated animals were determined and compared...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28427866/effect-of-amyloid-%C3%AE-25-35-in-hyperglycemic-and-hyperinsulinemic-rats-effects-on-phosphorylation-and-o-glcnacylation-of-tau-protein
#6
Liliana Lozano, Jorge Guevara, Tony Lefebvre, Ivan Ramos-Martinez, Daniel Limón, Alfonso Díaz, Eduarda Cerón, Edgar Zenteno
Aggregation of the amyloid beta (Aβ) peptide and hyperphosphorylation of tau protein, which are markers of Alzheimer's disease (AD), have been reported also in diabetes mellitus (DM). One regulator of tau phosphorylation is O-GlcNAcylation, whereas for hyperphosphorylation it could be GSK3beta, which is activated in hyperglycemic conditions. With this in mind, both O-GlcNAcylation and phosphorylation of tau protein were evaluated in the brain of rats with streptozotocin (STZ)-induced hyperglycemia and hyperinsulinemia and treated with the Aß25-35 peptide in the hippocampal region CA1...
April 6, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28424791/antifatigue-effects-of-antrodia-cinnamomea-cultured-mycelium-via-modulation-of-oxidative-stress-signaling-in-a-mouse-model
#7
Yange Liu, Lanzhou Li, Shengshu An, Yuanzhu Zhang, Shiwei Feng, Lu Zhao, Lirong Teng, Di Wang
Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects. In this study, we aim to assess whether the antifatigue effects of A. cinnamomea mycelia (AC) and its underlying mechanisms are related to oxidative stress signaling using behavioral mouse models and biochemical indices detection. Mice were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks. AC had no effect on the spontaneous activities of mice indicating its safety on central nervous system. Furthermore, results obtained from weight-loaded forced swimming test, rotary rod test, and exhausted running test confirmed that AC significantly enhanced exercise tolerance of mice...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28424497/the-glycogen-synthase-kinase-mogsk1-regulated-by-mps1-map-kinase-is-required-for-fungal-development-and-pathogenicity-in-magnaporthe-oryzae
#8
Tengsheng Zhou, Yasin F Dagdas, Xiaohan Zhu, Shiqin Zheng, Liqiong Chen, Zachary Cartwright, Nicholas J Talbot, Zonghua Wang
Magnaporthe oryzae, the causal agent of blast disease, is one of the most destructive plant pathogens, causing significant yield losses on staple crops such as rice and wheat. The fungus infects plants with a specialized cell called an appressorium, whose development is tightly regulated by MAPK signaling pathways following the activation of upstream sensors in response to environmental stimuli. Here, we show the expression of the Glycogen synthase kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly under the stressed conditions...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423558/biological-basis-and-clinical-study-of-glycogen-synthase-kinase-3%C3%AE-targeted-therapy-by-drug-repositioning-for-glioblastoma
#9
Takuya Furuta, Hemragul Sabit, Yu Dong, Katsuyoshi Miyashita, Masashi Kinoshita, Naoyuki Uchiyama, Yasuhiko Hayashi, Yutaka Hayashi, Toshinari Minamoto, Mitsutoshi Nakada
BACKGROUND: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423281/moringa-olifera-leaves-aqueous-extract-ameliorates-hepatotoxicity-in-alloxan-induced-diabetic-rats
#10
Mabrouk Attia Abd Eldaim, Ahmed Shaban, Samy Abd Elaziz
This study was carried out to evaluate the possible mechanisms through which the Moringa oleifera leaves aqueous extract reveals its hepatoprotective effects in alloxan induced diabetic rats. Eighty albino rats were assigned into four groups. The control group was given sterile saline. The second group was injected with alloxan (150 mg/kg BW) i.p. The third group was given Moringa oleifera leaves aqueous extract (250 mg/kg BW) orally daily. The fourth group was injected with alloxan as the second group and administrated Moringa oleifera leaves aqueous extract as in the third group...
April 19, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28422872/effect-of-hsp27-and-cofilin-in-the-injury-of-hypoxia-reoxygenation-on-hepatocyte-membrane-f-actin-microfilaments
#11
Yafei Zhang, Jiazhong Wang, Hong Ji, Hongwei Lu, Le Lu, Jinlong Wang, Yiming Li
Hypoxia-reoxygenation (H/R) injury hepatocyte models were established to simulate the ischemia/reperfusion injury of transplanted organ. Through the study of the molecular mechanism of H/R on the F-actin damage of the liver cytomembrane, the mechanism of F-actin damage induced by ischemia and reperfusion was studied from the level of cell and molecule.The hypoxic environment of cells in vitro was simulated by chemical hypoxia agent CoCl2. Liver cells were detected by MTT, H/R group was subdivided into 3 subgroups: H/R 2, 4, and 6 h...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28422159/spastic-paraplegia-linked-phospholipase-papla1-is-necessary-for-development-reproduction-and-energy-metabolism-in-drosophila
#12
Martina Gáliková, Peter Klepsatel, Judith Münch, Ronald P Kühnlein
The human PAPLA1 phospholipase family is associated with hereditary spastic paraplegia (HSP), a neurodegenerative syndrome characterized by progressive spasticity and weakness of the lower limbs. Taking advantage of a new Drosophila PAPLA1 mutant, we describe here novel functions of this phospholipase family in fly development, reproduction, and energy metabolism. Loss of Drosophila PAPLA1 reduces egg hatchability, pre-adult viability, developmental speed, and impairs reproductive functions of both males and females...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#13
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421373/role-of-glycogen-synthase-kinase-following-myocardial-infarction-and-ischemia-reperfusion
#14
REVIEW
S Ghaderi, N Alidadiani, N Dilaver, H R Heidari, R Parvizi, R Rahbarghazi, J Soleimani-Rad, B Baradaran
Glycogen synthase kinase-3 beta (GSK3β) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3β is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3β is involved in several pathways leading to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease...
April 18, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28421199/valproic-acid-protects-primary-dopamine-neurons-from-mpp-induced-neurotoxicity-involvement-of-gsk3%C3%AE-phosphorylation-by-akt-and-erk-through-the-mitochondrial-intrinsic-apoptotic-pathway
#15
Chi Zhang, Xianrui Yuan, Zhongliang Hu, Songlin Liu, Haoyu Li, Ming Wu, Jian Yuan, Zijin Zhao, Jun Su, Xiangyu Wang, Yiwei Liao, Qing Liu
Valproic acid (VPA), a drug widely used to treat manic disorder and epilepsy, has recently shown neuroprotective effects in several neurological diseases, particularly in Parkinson's disease (PD). The goal of the present study was to confirm VPA's dose-dependent neuroprotective propensities in the MPP(+) model of PD in primary dopamine (DA) neurons and to investigate the underlying molecular mechanisms using specific mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase- (PI3K-) Akt signaling inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28419828/hypoglycemic-and-hypolipidemic-effects-of-a-polysaccharide-from-flower-buds-of-lonicera-japonica-in-streptozotocin-induced-diabetic-rats
#16
Dongying Wang, Xiangmei Zhao, Yulan Liu
Hyperglycemia and dyslipidemia are classic features for diabetes mellitus (DM). In this study, one fraction of the crude polysaccharides extracted from Lonicera japonica flower buds (LJP) were investigated for its hypolipidaemic and hypoglycaemic activities by means of streptozotocin (STZ)-inducd diabetic rats. Interestingly, after orally administrated with 800mg/kg body weight (B.W.) LJP for 42 days, the food and water intake and the levels of sugar and insulin in blood for the diatebic rats were drastically decreased, while the contents of liver and skeletal muscle glycogen and the concentrations of hepatic pyruvate kinase and hexokinase were obviously increased (p<0...
April 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28419608/multiple-breath-hold-proton-spectroscopy-of-human-liver-at-3t-relaxation-times-and-concentrations-of-glycogen-choline-and-lipids
#17
Jan Weis, Joel Kullberg, Håkan Ahlström
PURPOSE: To evaluate the feasibility of an expiration multiple breath-hold (1) H-MRS technique to measure glycogen (Glycg), choline-containing compounds (CCC), and lipid relaxation times T1 , T2 , and their concentrations in normal human liver. MATERIALS AND METHODS: Thirty healthy volunteers were recruited. Experiments were performed at 3T. Multiple expiration breath-hold single-voxel point-resolved spectroscopy (PRESS) technique was used for localization. Water-suppressed spectra were used for the estimation of Glycg, CCC, lipid methylene (CH2 )n relaxation times and concentrations...
April 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28419226/sugar-versus-fat-elimination-of-glycogen-storage-improves-lipid-accumulation-in-yarrowia-lipolytica
#18
Govindprasad Bhutada, Martin Kavšcek, Rodrigo Ledesma-Amaro, Stéphane Thomas, Gerald N Rechberger, Jean-Marc Nicaud, Klaus Natter
Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon storage in most eukaryotic organisms. We investigated the glycogen metabolism of the oleaginous Y. lipolytica and found that this yeast accumulates up to 16% glycogen in its biomass. Assuming that elimination of glycogen synthesis would result in an improvement of lipid accumulation, we characterized and deleted the single gene coding for glycogen synthase, YlGSY1. The mutant was grown under lipogenic conditions with glucose and glycerol as substrates and we obtained up to 60% improvement in TAG accumulation compared to the wild type strain...
April 17, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#19
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/28417372/separation-and-visualization-of-glycans-by-fluorophore-assisted-carbohydrate-electrophoresis
#20
Mélissa Robb, Joanne K Hobbs, Alisdair B Boraston
Fluorophore-assisted carbohydrate electrophoresis (FACE) is a method in which a fluorophore is covalently attached to the reducing end of carbohydrates, thereby allowing visualization following high-resolution separation by electrophoresis. This method can be used for carbohydrate profiling and sequencing, as well as for the determination of the specificity of carbohydrate-active enzymes. Here, we describe and demonstrate the use of FACE to separate and visualize the glycans released following digestion of oligosaccharides by glycoside hydrolases (GHs) using two examples: (1) the digestion of chitobiose by the streptococcal β-hexosaminidase GH20C, and (2) the digestion of glycogen by the GH13 member SpuA...
2017: Methods in Molecular Biology
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