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https://www.readbyqxmd.com/read/28098360/morroniside-a-secoiridoid-glycoside-from-cornus-officinalis-attenuates-neuropathic-pain-by-activation-of-spinal-glucagon-like-peptide-1-receptors
#1
Meng Xu, Hai-Yun Wu, Hao Liu, Nian Gong, Yi-Rui Wang, Yong-Xiang Wang
BACKGROUND AND PURPOSE: Iridoid glycosides with intact double bond scaffold of cyclopentapyran were reversible and orthosteric agonists of glucagon-like peptide-1 (GLP-1) receptors and possess antinociception and neuroprotection. Morroniside, derived from the medicinal herb Cornus officinalis, is an atypical secoiridoid replaced by a six-membered cyclic inner ether fragment. This study investigated whether morroniside was an orthosteric GLP-1 receptor agonist and had antihypersensitivity activities in neuropathy...
January 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28098164/uncovering-the-sumoylation-and-ubiquitylation-crosstalk-in-human-cells-using-sequential-peptide-immunopurification
#2
Frédéric Lamoliatte, Francis P McManus, Ghizlane Maarifi, Mounira K Chelbi-Alix, Pierre Thibault
Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096338/mitochondrial-fusion-dynamics-is-robust-in-the-heart-and-depends-on-calcium-oscillations-and-contractile-activity
#3
Verónica Eisner, Ryan R Cupo, Erhe Gao, György Csordás, William S Slovinsky, Melanie Paillard, Lan Cheng, Jessica Ibetti, S R Wayne Chen, J Kurt Chuprun, Jan B Hoek, Walter J Koch, György Hajnóczky
Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes. Promptly after isolation, cardiomyocytes showed extensive mitochondrial connectivity and fusion, which decayed in culture (at 24-48 h)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28094839/improved-fluorescence-assays-to-measure-the-defects-associated-with-f508del-cftr-allow-identification-of-new-active-compounds
#4
Emily Langron, Michela I Simone, Clémence M S Delalande, Jean-Louis Reymond, David L Selwood, Paola Vergani
BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a Cl-/HCO3 - channel. F508del, the most common CF-associated mutation, causes both gating and biogenesis defects in the CFTR protein. This paper describes the optimisation of two fluorescence assays, capable of measuring CFTR function and cellular localisation, and their use in a pilot drug screen. EXPERIMENTAL APPROACH: HEK293 cells expressing YFP-F508del-CFTR, in which halide sensitive YFP is tagged to the N-terminal of CFTR, were used to screen a small library of compounds based on the VX-770 scaffold...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28093031/the-inhibitory-effects-of-five-alkaloids-on-the-substrate-transport-mediated-through-human-organic-anion-and-cation-transporters
#5
Tahiatul Shams, Xiaoxi Lu, Ling Zhu, Fanfan Zhou
1. Human Solute Carrier Transporters (SLCs) are important membrane proteins mediate the cellular transport of many endogenous and exogenous substances. Organic anion/cation transporters (OATs/OCTs) and Organic anion transporting polypeptides (OATPs) are essential SLCs involved in drug influx. Drug-drug/herb interactions through competing for specific SLCs often lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In this study we comprehensively investigated the inhibitory effects of five clinically relevant alkaloids (dendrobine, matrine, oxymatrine, tryptanthrin and chelerythrine) on the substrate transport through several OATs/OCTs and OATPs...
January 17, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28090274/the-role-of-m2000-as-an-anti-inflammatory-agent-in-toll-like-receptor-2-microrna-155-pathway
#6
Fatemeh Pourgholi, Mahsa Hajivalili, Rasoul Razavi, Shadi Esmaeili, Behzad Baradaran, Ali Akbar Movasaghpour, Sanam Sadreddini, Hamidreza Goodarzynejad, Abbas Mirshafiey, Mehdi Yousefi
BACKGROUND: M2000 is a newly designed and safe Non-Steroidal Anti-Inflammatory Drug (NSAID). The aim of this study was to assess the effects of M2000 on expression levels of Suppressor of Cytokine Signaling-1 (SOCS-1) and Src Homology-2 domain-containing inositol-5'-phosphatase 1 (SHIP1) proteins via Toll-Like Receptor (TLR) 2/microRNA-155 pathway. METHODS: HEK293 TLR2 cell line and Peripheral Blood Mononuclear Cells (PBMCs) were treated by different concentrations of M2000 in MTT assay...
January 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28089882/a-highly-efficient-modified-human-serum-albumin-signal-peptide-to-secrete-proteins-in-cells-derived-from-different-mammalian-species
#7
Carolina Attallah, Marina Etcheverrigaray, Ricardo Kratje, Marcos Oggero
Signal peptides (SPs) are key elements in the production of recombinant proteins; however, little information is available concerning different SP in mammalian cells other than CHO. In order to study the efficiency of different SPs to direct the traffic along the secretory pathway of the green fluorescence protein (GFP) and a scFv-Fc fusion protein; CHO-K1, HEK293 and NS0 cell lines were transfected in a transient and stable way. SP of human azurocidin (AZ), modified human albumin (mSA), modified Cricetulus griseus Ig kappa chain V III region MOPC 63 like (mIgκ C) and modified human Ig kappa chain V III region VG (mIgκ H) were evaluated...
January 10, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28088389/nalfurafine-is-a-g-protein-biased-agonist-having-significantly-greater-bias-at-the-human-than-rodent-form-of-the-kappa-opioid-receptor
#8
Selena S Schattauer, Jamie R Kuhar, Allisa Song, Charles Chavkin
Nalfurafine is a moderately selective kappa opioid receptor (KOR) analgesic with low incidence of dysphoric side effects in clinical development for the treatment of uremic pruritis. The basis for its reduced dysphoric effect compared to other KOR agonists is not clear, but prior studies suggest that the aversive properties of KOR agonists require p38α MAPK activation through an arrestin-dependent mechanism. To determine whether nalfurafine is a functionally selective KOR agonist, we measured its potency to activate the G protein-dependent early phase of Extracellular Signal-Regulated Kinase (ERK1/2) phosphorylation and the arrestin-dependent late phase of p38 MAPK signaling...
January 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28081499/screening-active-compounds-from-corydalis-yanhusuo-by-combining-high-expression-vegf-receptor-hek293-cell-membrane-chromatography-with-hplc-esi-it-tof-msn-method
#9
Fen Wei, Qi Hu, Jing Huang, Shengli Han, Sicen Wang
Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay...
January 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28078343/differential-effects-of-silver-and-iron-oxide-nanoparticles-on-iapp-amyloid-aggregation
#10
Miaoyi Wang, Aleksandr Kakinen, Emily H Pilkington, Thomas P Davis, Pu Chun Ke
Recent studies have shown promise on the use of small molecules and nanoparticles (NPs) for the inhibition of protein aggregation, a hallmark of neurodegenerative diseases and type 2 diabetes (T2D). Towards this end here we show the differential effects of silver and iron oxide nanoparticles (AgNPs and IONPs) on the mesoscopic properties of human islet amyloid polypeptide (IAPP) aggregation associated with T2D. Both citrate- and branched polyethyleneimine-coated AgNPs (c-AgNPs, bPEI-AgNPs) inhibited IAPP aggregation at 500 μg mL(-1), likely through electrostatic attraction and sequestering of IAPP monomers from fibrillation...
January 12, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28078247/effects-of-biebersteinia-multifida-hydro-ethanol-extract-on-proliferation-and-apoptosis-of-human-prostate-cancer-and-human-embryonic-kidney-cells
#11
Alireza Golshan, Samira Hassanzadeh, Maryam Mojdekanloo, Zahra Tayarani-Najaran
OBJECTIVE: Biebersteinia (Geraniaceae) has a history of use in traditional medicine in some countries including Iran. In the present study, cytotoxic and apoptogenic properties of hydro-ethanol extract of B. multifidi was investigated on human prostate cancer cell lines (PC3 and DU 145) and human embryonic kidney 293 (HEK293) cells. MATERIALS AND METHODS: Cells were cultured in RPMI-1640 medium supplemented with 10% FBS at 37ºC in a humidified atmosphere of 95% air and 5% CO2...
November 2016: Avicenna Journal of Phytomedicine
https://www.readbyqxmd.com/read/28077648/human-papillomavirus-16-e6-up-regulates-apobec3b-via-the-tead-transcription-factor
#12
Seiichiro Mori, Takamasa Takeuchi, Yoshiyuki Ishii, Takashi Yugawa, Tohru Kiyono, Hiroshi Nishina, Iwao Kukimoto
: The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077578/novel-serine-176-phosphorylation-of-ybx1-activates-nf-%C3%AE%C2%BAb-in-colon-cancer
#13
Matthew Martin, Laiqing Hua, Benlian Wang, Han Wei, Lakshmi Prabhu, Antja-Voy Hartley, Guanglong Jiang, Yunlong Liu, Tao Lu
The Y box protein 1 (YBX1) is a well-known oncoprotein which has tumor promoting functions. YBX1 is widely considered to be an attractive therapeutic target in cancer. In order to develop novel therapeutics to target YBX1, it is of great importance to understand how YBX1 is finely regulated in cancer. Previously, we have shown that YBX1 could function as a tumor promoter through phosphorylation of its serine 165 (S165) residue, leading to the activation of the NF-[kappa]B signaling pathway (1). In this study, using mass spectrometry analysis, we discovered a quite distinct phosphorylation site, S176, on YBX1...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28070108/pathway-of-3-mcpd-induced-apoptosis-in-human-embryonic-kidney-cells
#14
Jian Ji, Pei Zhu, Chao Sun, Jiadi Sun, Lu An, Yinzhi Zhang, Xiulan Sun
3-Chloropropane-1,2-diol (3-MCPD) is a heat-produced contaminant formed during the preparation of soy sauce worldwide. The present investigation was conducted to determine the molecular aspects of 3-MCPD toxicity on human embryonic kidney cells (HEK293). Cell viability and apoptosis were assessed in response to exposure to 3-MCPD using the MTT assay and high-content screening (HCS). DNA damage, intracellular reactive oxygen species (ROS) and apoptosis-related proteins were evaluated. Genes related with apoptosis were detected by qPCR-array for further understanding the 3-MCPD induced cell apoptosis signaling pathway...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069442/novel-signaling-of-dynorphin-at-%C3%AE%C2%BA-opioid-receptor-bradykinin-b2-receptor-heterodimers
#15
Bingyuan Ji, Haiqing Liu, Rumin Zhang, Yunlu Jiang, Chunmei Wang, Sheng Li, Jing Chen, Bo Bai
The κ-opioid receptor (KOR) and bradykinin B2 receptor (B2R) are involved in a variety of important physiological processes and share many similar characteristics in terms of their distribution and functions in the nervous system. We first demonstrated the endogenous expression of KOR and B2R in human SH-SY5Y cells and their co-localization on the membrane of human embryonic kidney 293 (HEK293) cells. Bioluminescence and fluorescence resonance energy transfer and the proximity ligation assay were exploited to demonstrate the formation of functional KOR and B2R heteromers in transfected cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28068943/a-case-of-gabar-antibodies-in-schizophrenia
#16
Ida S Haussleiter, Klaus-Peter Wandinger, Georg Juckel
BACKGROUND: In the last couple of years, schizophrenia was often discussed as autoimmune disease. Several antibodies were suspected, but so far there has been no proof of Gamma-aminobutyric acid (GABA) receptor antibodies in patients with schizophrenia. CASE PRESENTATION: In this case report we present a 21-year old woman with schizophrenic symptoms, who showed anti-GABAB1 antibodies when screened by a vast recombinant neurology mosaic on Human Embryonic Kidney Cells 293 (HEK293) cells...
January 10, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28068367/cell-surface-integrins-and-car-are-both-essential-for-adenovirus-type-5-transduction-of-canine-cells-of-lymphocytic-origin
#17
Payal Agarwal, Elizabeth A Gammon, Abdul Mohin Sajib, Maninder Sandey, Bruce F Smith
Adenoviruses are the most widely used vectors in cancer gene therapy. Adenoviruses vectors are well characterized and are easily manipulated. Adenovirus serotype 5 (Ad5) is the most commonly used human serotype. Ad5 internalization into host cells is a combined effect of binding of Ad5 fiber knob with the coxsackie virus and adenovirus receptor (CAR) and binding of RGD motifs in viral penton to cell surface integrins (αvβ3, αvβ5). Ad5's wide range of host-cell transduction and lack of integration into the host genome have made it an excellent choice for cancer therapeutics...
2017: PloS One
https://www.readbyqxmd.com/read/28068062/sequence-defined-backbone-modifications-regulate-antibacterial-activity-of-oligoteas
#18
Mintu Porel, Dana N Thornlow, Christine M Artim, Christopher A Alabi
In response to the urgent need for new antibiotic development strategies, antimicrobial peptides (AMPs) and other synthetic polymers are being actively investigated as promising alternatives to traditional antibiotics. Although most AMPs display lytic activity against several types of bacteria, they have poor toxicology profiles and are susceptible to proteolysis in vivo. While many synthetic variants have been created to mimic AMPs by tuning the hydrophobic to cationic ratio of the side-chain groups, few have decoupled the effects of charge from hydrophobicity in discrete systems, and none have investigated the effect of backbone hydrophobicity...
January 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28066143/acepromazine-inhibits-herg-potassium-ion-channels-expressed-in-human-embryonic-kidney-293-cells
#19
Young Shin Joo, Hong Joon Lee, Jin-Sung Choi, Ki-Wug Sung
The effects of acepromazine on human ether-à-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an IC50 value of 1.5 µM and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28065721/the-key-residue-within-the-second-extracellular-loop-of-human-ep3-involved-in-selectively-turning-down-pge2-and-retaining-pge1-mediated-signaling-in-live-cells
#20
Hironari Akasaka, Natasha Thaliachery, Xianghai Zheng, Marissa Blumenthal, Sameer Nikhar, Emma E Murdoch, Qinglan Ling, Ke-He Ruan
Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts...
January 5, 2017: Archives of Biochemistry and Biophysics
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