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PTP1B

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https://www.readbyqxmd.com/read/28744004/sirt1-negatively-regulates-fc%C3%AE%C2%B5ri-mediated-mast-cell-activation-through-ampk-and-ptp1b-dependent-processes
#1
Xian Li, Youn Ju Lee, Fansi Jin, Young Na Park, Yifeng Deng, Youra Kang, Ju Hye Yang, Jae-Hoon Chang, Dong-Young Kim, Jung-Ae Kim, Young-Chae Chang, Hyun-Jeong Ko, Cheorl-Ho Kim, Makoto Murakami, Hyeun Wook Chang
Sirt1, a key regulator of metabolism and longevity, has recently been implicated in the regulation of allergic reactions, although the underlying mechanism remains unclear. Here we show that Sirt1 negatively regulates FcεRI-stimulated mast cell activation and anaphylaxis through two mutually regulated pathways involving AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B). Mast cell-specific knockout of Sirt1 dampened AMPK-dependent suppression of FcεRI signaling, thereby augmenting mast cell activation both in vitro and in vivo...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732860/structure-features-and-in-vitro-hypoglycemic-activities-of-polysaccharides-from-different-species-of-maidong
#2
Yajun Gong, Jie Zhang, Fei Gao, Jiewen Zhou, Zhinan Xiang, Chenggao Zhou, Luosheng Wan, Jiachun Chen
Structures and in vitro hypoglycemic activities of polysaccharides from different species of Maidong were studied. The primary structures of polysaccharides were elucidated on the basis of GC, GC-MS, infrared, NMR and periodate oxidation-Smith degradation. Liriope spicata polysaccharide (LSP), Ophiopogon japonicus polysaccharide (OJP) and Liriope muscari polysaccharide (LMP) were composed of β-fructose and α-glucose. The average molecular weights of LSP, OJP and LMP were 4742, 4925 and 4138Da with polydispersity indexes of 1...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28729389/severe-energy-deficit-up-regulates-leptin-receptors-leptin-signaling-and-ptp1b-in-human-skeletal-muscle
#3
Ismael Perez-Suarez, Jesus Gustavo Ponce-Gonzalez, Jaime de La Calle-Herrero, Jose Losa-Reyna, Marcos Martin-Rincon, David Morales-Alamo, Alfredo Santana, Hans-Christer Holmberg, Jose A L Calbet
In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are down-regulated. To determine whether OBR and leptin signaling are up-regulated with a severe energy deficit fifteen overweight men were assessed before (PRE), after 4 days of caloric restriction (3.2 Kcal/kg BW/day) in combination with prolonged exercise (CRE) (8h walking + 45min single-arm cranking/day) to induce an energy deficit of ~5500 Kcal/d, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n=8) or sucrose (n=7) (0...
July 20, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28726759/high-resolution-inhibition-profiling-combined-with-hplc-hrms-spe-nmr-for-identification-of-ptp1b-inhibitors-from-vietnamese-plants
#4
Binh Thi Dieu Trinh, Anna K Jäger, Dan Staerk
Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator in insulin signal transduction by deactivating the insulin receptor. Thus, PTP1B inhibition has emerged as a potential therapeutic strategy for curing insulin resistance. In this study, 40 extracts from 18 different plant species were investigated for PTP1B inhibitory activity in vitro. The most promising one, the EtOAc extract of Ficus racemosa, was investigated by high-resolution PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR analysis...
July 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28707052/steered-molecular-dynamics-for-investigating-the-interactions-between-insulin-receptor-tyrosine-kinase-irk-and-variants-of-protein-tyrosine-phosphatase-1b-ptp1b
#5
Hung Nguyen, Nhat Do, Tuyn Phan, Tri Pham
The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK...
July 13, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28703596/rhodomollanol-a-a-highly-oxygenated-diterpenoid-with-a-5-7-5-5-tetracyclic-carbon-skeleton-from-the-leaves-of-rhododendron-molle
#6
Junfei Zhou, Guanqun Zhan, Hanqi Zhang, Qihua Zhang, Ying Li, Yongbo Xue, Guangmin Yao
A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1), and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the leaves of Rhododendron molle. Their structures were elucidated using comprehensive spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5 hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated with three cyclopentane units. The plausible biosynthetic pathway for 1 was proposed...
July 13, 2017: Organic Letters
https://www.readbyqxmd.com/read/28699753/identification-of-anthocyanins-from-four-kinds-of-berries-and-their-inhibition-activity-to-%C3%AE-glycosidase-and-protein-tyrosine-phosphatase-1b-by-hplc-ft-icr-ms-ms
#7
Ting Xiao, Zhenghong Guo, Baoshan Sun, Yuqing Zhao
The polyphenolic profiles of four berries (blueberry, bilberry, mulberry, and cranberry) in China were investigated using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Thirty-nine polyphenols including 26 anthocyanins, 9 flavonoids, and 4 phenolic acids were identified accurately. Cyanidin aglycones are common in four berries, and malvidin aglycones are the main compounds found in bilberry and cranberry. The anthocyanin level in blueberry are the highest with 739.6 ± 17.14 mg/g DW and presented the strongest antioxidant capacity in DPPH, ABTS, FRAP, and ORAC assay...
July 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28690198/punicalagin-a-ptp1b-inhibitor-induces-m2c-phenotype-polarization-via-up-regulation-of-ho-1-in-murine-macrophages
#8
Xiaolong Xu, Yuhong Guo, Jingxia Zhao, Shasha He, Yan Wang, Yan Lin, Ning Wang, Qingquan Liu
Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC50 value of 1.04μM. Results from NPOI further showed that the Kon and Koff of PUN-PTP1B complex were 3.38e2M(-1)s(-1) and 4.13e-3s(-1), respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation...
July 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28686728/regulation-of-platelet-activating-factor-mediated-protein-tyrosine-phosphatase-1b-activation-by-a-janus-kinase-2-calpain-pathway
#9
Geneviève Hamel-Côté, Daniel Gendron, Marek Rola-Pleszczynski, Jana Stankova
Atherosclerosis is a pro-inflammatory condition underlying many cardiovascular diseases. Platelet-activating factor (PAF) and interleukin 6 (IL-6) are actively involved in the onset and progression of atherosclerotic plaques. The involvement of monocyte-derived macrophages is well characterized in the installation of inflammatory conditions in the plaque, but less is known about the contribution of monocyte-derived dendritic cells (Mo-DCs). In the same way, the involvement of calcium, phospholipase C and A2 in PAF-induced IL-6 production, in different cells types, has been shown; however, the importance of the Jak/STAT pathway and its regulation by protein-tyrosine phosphatases in this response have not been addressed...
2017: PloS One
https://www.readbyqxmd.com/read/28684416/thioredoxin-reductase-1-and-nadph-directly-protect-protein-tyrosine-phosphatase-1b-from-inactivation-during-h2o2-exposure
#10
Markus Dagnell, Paul E Pace, Qing Cheng, Jeroen Frijhoff, Arne Östman, Elias S J Arnér, Mark B Hampton, Christine C Winterbourn
Regulation of growth factor signaling involves reversible inactivation of protein tyrosine phosphatases (PTPs) through the oxidation and reduction of their active site cysteine. However, there is limited mechanistic understanding of these redox events and their coordination in the presence of cellular antioxidant networks. Here, we investigated interactions between PTP1B and the peroxiredoxin 2 (Prx2)/thioredoxin 1 (Trx1)/thioredoxin reductase 1 (TrxR1) network. We found that Prx2 becomes oxidized in PDGF-treated fibroblasts, but only when TrxR1 has first been inhibited...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28680757/downregulation-of-ptp1b-and-tc-ptp-phosphatases-potentiate-dendritic-cell-based-immunotherapy-through-il-12-ifn%C3%AE-signaling
#11
Claudia Penafuerte, Matthew Feldhammer, John R Mills, Valerie Vinette, Kelly A Pike, Anita Hall, Eva Migon, Gerard Karsenty, Jerry Pelletier, George Zogopoulos, Michel L Tremblay
PTP1B and TC-PTP are highly related protein-tyrosine phosphatases (PTPs) that regulate the JAK/STAT signaling cascade essential for cytokine-receptor activation in immune cells. Here, we describe a novel immunotherapy approach whereby monocyte-derived dendritic cell (moDC) function is enhanced by modulating the enzymatic activities of PTP1B and TC-PTP. To downregulate or delete the activity/expression of these PTPs, we generated mice with PTP-specific deletions in the dendritic cell compartment or used PTP1B and TC-PTP specific inhibitor...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28676388/four-new-neolignans-isolated-from-eleutherococcus-senticosus-and-their-protein-tyrosine-phosphatase-1b-inhibitory-activity-ptp1b
#12
Le Zhang, Ban-Ban Li, Hao-Ze Li, Xiao Meng, Xin Lin, Yi-Yu Jiang, Jong-Seog Ahn, Long Cui
Four new compounds, erythro-7'E-4-hydroxy-3,3'-dimethoxy-8,5'-oxyneoligna-7'-ene-7,9-diol-9'-al (1), (7S,8S)-4-hydroxy-3,1',3'-trimethoxy-4',7-epoxy-8,5'-neolign-9-ol (5), (7S,8S,7'E)-5-hydroxy-3,3'-dimethoxy-4',7-epoxy-8,5'-neolign-7'-ene-9,9'-diol (6) and (7S,8S,7'E)-5-hydroxy-3,3',9'-trimethoxy-4'-7-epoxy-8,5'-neolign-7'-ene-9-ol (7). Along with four known compounds (2-4, 8) were isolated from the EtOAc-soluble extract of Eleutherococcus senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses...
July 1, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28673968/hepatic-zip14-mediated-zinc-transport-is-required-for-adaptation-to-endoplasmic-reticulum-stress
#13
Min-Hyun Kim, Tolunay B Aydemir, Jinhee Kim, Robert J Cousins
Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14(-/-) (KO) mice, which exhibit impaired hepatic zinc uptake...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28662582/further-new-gypenosides-from-jiaogulan-gynostemma-pentaphyllum
#14
Jun Wang, Jun-Li Yang, Pan-Pan Zhou, Xian-Hua Meng, Yan-Ping Shi
Jiaogulan (Gynostemma pentaphyllum) has been widely used as a herbal tea, dietary supplement, and vegetable in Asian countries. In this study, six new gypenosides (1-6) were isolated from the aerial parts of G. pentaphyllum. Their molecular structures were elucidated through spectroscopic analysis and acid hydrolysis. Gypenosides 1 and 2 represented the first example of a dammar-21-O- glucopyranoside without any unsaturated functional group and a dammar-3-O-glucopyranosyl-25-O-glucopyranoside without any cyclization in the side chain, respectively...
July 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28642102/varic-acid-analogues-from-fungus-as-ptp1b-inhibitors-biological-evaluation-and-structure-activity-relationships
#15
Wenlong Sun, Chunlin Zhuang, Xia Li, Bowei Zhang, Xinhua Lu, Zhihui Zheng, Yuesheng Dong
Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28639351/titanium-released-from-dental-implant-enhances-pre-osteoblast-adhesion-by-ros-modulating-crucial-intracellular-pathways
#16
M C Rossi, Fjb Bezerra, R A Silva, B P Crulhas, Cjc Fernandes, A S Nascimento, V A Pedrosa, P Padilha, W F Zambuzzi
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p<0...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#17
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28625849/leveraging-reciprocity-to-identify-and-characterize-unknown-allosteric-sites-in-protein-tyrosine-phosphatases
#18
Danica S Cui, Victor Beaumont, Patrick S Ginther, James M Lipchock, J Patrick Loria
Drug-like molecules targeting allosteric sites in proteins are of great therapeutic interest; however, identification of potential sites is not trivial. A straightforward approach to identify hidden allosteric sites is demonstrated in protein tyrosine phosphatases (PTP) by creation of single alanine mutations in the catalytic acid loop of PTP1B and VHR. This approach relies on the reciprocal interactions between an allosteric site and its coupled orthosteric site. The resulting NMR chemical shift perturbations (CSPs) of each mutant reveal clusters of distal residues affected by acid loop mutation...
July 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28624142/anti-diabetic-xanthones-from-the-bark-of-garcinia-xanthochymus
#19
Chi N Nguyen, Binh T D Trinh, Toan B Tran, Le-Thu T Nguyen, Anna K Jäger, Lien-Hoa D Nguyen
An ethyl acetate extract the bark of Garcinia xanthochymus exhibited strong inhibition towards α-glucosidase and PTP1B with IC50 values of 0.3±0.1μg/mL and 2.3±0.4μg/mL, respectively. Chemical constituents of the extract were therefore examined, and two new compounds, xanthochymusxanthones A (1) and B (2), along with ten known xanthones (3-12), were isolated. Their structures were determined using spectroscopic methods, mainly 1D and 2D NMR. Inhibitory activity of the isolated compounds was then tested, and subelliptenone F (12) showed significant effect towards α-glucosidase with IC50 value of 4...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28608833/potential-of-icariin-metabolites-from-epimedium-koreanum-nakai-as-antidiabetic-therapeutic-agents
#20
Da Hye Kim, Hyun Ah Jung, Hee Sook Sohn, Jin Woong Kim, Jae Sue Choi
The therapeutic properties of Epimediumkoreanum are presumed to be due to the flavonoid component icariin, which has been reported to have broad pharmacological potential and has demonstrated anti-diabetic, anti-Alzheimer's disease, anti-tumor, and hepatoprotective activities. Considering these therapeutic properties of icariin, its deglycosylated icaritin and glycosylated flavonoids (icaeriside II, epimedin A, epimedin B, and epimedin C) were evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase...
June 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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