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https://www.readbyqxmd.com/read/28933230/inhibition-of-protein-tyrosine-phosphatase-ptp1b-and-%C3%AE-glucosidase-by-geranylated-flavonoids-from-paulownia-tomentosa
#1
Yeong Hun Song, Zia Uddin, Young Min Jin, Zuopeng Li, Marcus John Curtis-Long, Kwang Dong Kim, Jung Keun Cho, Ki Hun Park
Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1-8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1-5) and dihydroflavonols (6-8)...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28919207/phospho-regulation-of-soma-to-axon-transcytosis-of-neurotrophin-receptors
#2
Naoya Yamashita, Rajshri Joshi, Sheng Zhang, Zhong-Yin Zhang, Rejji Kuruvilla
Axonal targeting of signaling receptors is essential for neuronal responses to extracellular cues. Here, we report that retrograde signaling by target-derived nerve growth factor (NGF) is necessary for soma-to-axon transcytosis of TrkA receptors in sympathetic neurons, and we define the molecular underpinnings of this positive feedback regulation that enhances neuronal sensitivity to trophic factors. Activated TrkA receptors are retrogradely transported in signaling endosomes from distal axons to cell bodies, where they are inserted on soma surfaces and promote phosphorylation of resident naive receptors, resulting in their internalization...
September 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28917090/oleanane-triterpenes-with-protein-tyrosine-phosphatase-1b-inhibitory-activity-from-aerial-parts-of-lantana-camara-collected-in-indonesia-and-japan
#3
Delfly B Abdjul, Hiroyuki Yamazaki, Wilmar Maarisit, Henki Rotinsulu, Defny S Wewengkang, Deiske A Sumilat, Magie M Kapojos, Fitje Losung, Kazuyo Ukai, Michio Namikoshi
During the search for new protein tyrosine phosphatase (PTP) 1B inhibitors, EtOH extracts from the aerial parts of Lantana camara L. (lantana) collected at Manado (Indonesia) and two subtropical islands in Japan (Ishigaki and Iriomote Islands, Okinawa) exhibited potent inhibitory activities against PTP1B in an enzyme assay. Four previously undescribed oleanane triterpenes were isolated together with known triterpenes and flavones from the Indonesian lantana. The EtOH extracts of lantana collected in Ishigaki and Iriomote Islands exhibited different phytochemical profiles from each other and the Indonesian lantana...
September 13, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28916258/isoprenylated-phenolic-compounds-with-ptp1b-inhibition-from-morus-alba
#4
Qing-Hua Huang, Chun Lei, Pei-Pei Wang, Jing-Ya Li, Jia Li, Ai-Jun Hou
Two new Diels-Alder adducts, albasins A and B (1 and 2), one new isoprenylated 2-arylbenzofuran, albasin C (3), one new isoprenylated flavone, albasin D (4), together with sixteen known phenolic compounds, were isolated from the root bark of Morus alba. Their structures were elucidated by extensive spectroscopic analysis, including NMR, MS, and ECD data. All the new compounds and most of the known ones showed significant inhibitory effects on PTP1B in vitro with IC50 values ranging from 0.57 to 7.49μM.
September 12, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28899902/pharmacological-inhibition-of-protein-tyrosine-phosphatase-1b-ptp1b-protects-against-atherosclerotic-plaque-formation-in-the-ldlr-mouse-model-of-atherosclerosis
#5
Dawn Thompson, Nicola Morrice, Louise Grant, Samantha Le Sommer, Emma K Lees, Nimesh Mody, Heather M Wilson, Mirela Delibegovic
Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in LDLR(-/-) mouse model of atherosclerosis...
September 12, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28870898/inhibitory-activity-of-iron-chelators-ata-and-dfo-on-mcf-7-breast-cancer-cells-and-phosphatases-ptp1b-and-shp2
#6
Alicja Kuban-Jankowska, Kamlesh K Sahu, Magdalena Gorska-Ponikowska, Jack A Tuszynski, Michal Wozniak
BACKGROUND: Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). MATERIALS AND METHODS: We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28834433/meroterpenoids-with-protein-tyrosine-phosphatase-1b-inhibitory-activity-from-a-hyrtios-sp-marine-sponge
#7
Jie Wang, Feng-Rong Mu, Wei-Hua Jiao, Jian Huang, Li-Li Hong, Fan Yang, Ying Xu, Shu-Ping Wang, Fan Sun, Hou-Wen Lin
Three new meroterpenoids, hyrtiolacton A (1), nakijinol F (2), and nakijinol G (3), along with three known ones, nakijinol B (4), nakijinol E (5), and dactyloquinone A (6), were isolated and characterized from a Hyrtios sp. marine sponge collected from the South China Sea. The new structures were determined based on extensive analysis of HRESIMS and NMR data, and their absolute configurations were assigned by a combination of single-crystal X-ray diffraction and electronic circular dichroism analyses. Hyrtiolacton A (1) represents an unprecedented meroterpenoid featuring an unusual 2-pyrone attached to the sesquiterpene core, which is the first example of a pyrone-containing 4,9-friedodrimane-type sesquiterpene...
August 23, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28817487/inhibiting-protein-tyrosine-phosphatase-1b-to-improve-regenerative-functions-of-endothelial-cells
#8
Yuan Wang, Feng Yan, Wenjing Zhang, Shu Pang, Fan Jiang
Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor- and vascular endothelial growth factor receptor-dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration, and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28811203/bpn-a-marine-derived-ptp1b-inhibitor-activates-insulin-signaling-and-improves-insulin-resistance-in-c2c12-myotubes
#9
Qi Xu, Jiao Luo, Ning Wu, Renshuai Zhang, Dayong Shi
Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B...
August 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28807715/chrodrimanins-o-s-from-the-fungus-penicillium-sp-scs-kfd09-isolated-from-a-marine-worm-sipunculusnudus
#10
Fan-Dong Kong, Ren-Shuai Zhang, Qing-Yun Ma, Qing-Yi Xie, Pei Wang, Peng-Wei Chen, Li-Man Zhou, Hao-Fu Dai, Du-Qiang Luo, You-Xing Zhao
Five new meroterpenoids, chrodrimanins O-S (1-5), as well as a known one (6), were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus, from Haikou Bay, China. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Among them, compound 1 represents the first example of an unusual trichlorinated meroterpenoid with an unique dichlorine functionality...
August 12, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28754031/altered-protein-interactions-of-the-endogenous-interactome-of-ptpip51-towards-mapk-signaling
#11
Alexander Brobeil, Rajaa Chehab, Eric Dietel, Stefan Gattenlöhner, Monika Wimmer
Protein-protein interactions play a pivotal role in normal cellular functions as well as in carcinogenesis. The protein-protein interactions form functional clusters during signal transduction. To elucidate the fine calibration of the protein-protein interactions of protein tyrosine phosphatase interacting protein 51 (PTPIP51) a small molecule drug, namely LDC-3, directly targeting PTPIP51 is now available. Therefore, LDC-3 allows for the studying of the regulation of the endogenous interactome by modulating PTPIP51 binding capacity...
July 21, 2017: Biomolecules
https://www.readbyqxmd.com/read/28752048/myeloid-protein-tyrosine-phosphatase-1b-ptp1b-deficiency-protects-against-atherosclerotic-plaque-formation-in-the-apoe-mouse-model-of-atherosclerosis-with-alterations-in-il10-ampk%C3%AE-pathway
#12
D Thompson, N Morrice, L Grant, S Le Sommer, K Ziegler, P Whitfield, N Mody, H M Wilson, M Delibegović
OBJECTIVE: Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with Type 1 or Type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance due to impaired insulin receptor (IR) signaling. Moreover, inflammatory cells, in particular macrophages, play a key role in pathogenesis of atherosclerosis and insulin resistance in humans. We hypothesized that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR, specifically in macrophages, would have beneficial anti-inflammatory effects and lead to protection against atherosclerosis and CVD...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28744004/sirt1-negatively-regulates-fc%C3%AE%C2%B5ri-mediated-mast-cell-activation-through-ampk-and-ptp1b-dependent-processes
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
August 2, 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
#20
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
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