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https://www.readbyqxmd.com/read/28921993/lactam-stapled-cell-penetrating-peptides-cell-uptake-and-membrane-binding-properties
#1
Marco J Klein, Samuel Schmidt, Parvesh Wadhwani, Jochen Bürck, Johannes Reichert, Sergii Afonin, Marina Berditsch, Tim Schober, Roland Brock, Manfred Kansy, Anne S Ulrich
Stapling of side chains to stabilize an α-helical structure has been generally associated with an increased uptake of CPPs. Here, we compare 4 amphiphilic stapled peptides with their linear counterparts in terms of their membrane binding and conformational features, in order to correlate these with uptake efficiency and toxicological effects. The impact of lactam stapling was found to vary strongly with regard to the different aspects of peptide-membrane interactions. Nearly all stapled peptides caused less membrane perturbation (vesicle leakage, hemolysis, bacterial lysis) than their linear counterparts...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28920943/expression-function-and-regulation-of-the-embryonic-transcription-factor-tbx1-in-parathyroid-tumors
#2
Chiara Verdelli, Laura Avagliano, Vito Guarnieri, Filomena Cetani, Stefano Ferrero, Leonardo Vicentini, Edoardo Beretta, Alfredo Scillitani, Pasquale Creo, Gaetano Pietro Bulfamante, Valentina Vaira, Sabrina Corbetta
Transcription factors active in embryonic parathyroid cells can be maintained in adult parathyroids and be involved in tumorigenesis. TBX1, the candidate gene of 22q11.2-DiGeorge syndrome, which includes congenital hypoparathyroidism, is involved in parathyroid embryogenesis. The study aimed to investigate expression, function, and regulation of the parathyroid embryonic transcription factor TBX1 in human parathyroid adult normal and tumor tissues. TBX1 transcripts were detected in normal parathyroids and were deregulated in parathyroid tumors...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28917052/monitoring-of-methionine-sulfoxide-content-and-methionine-sulfoxide-reductase-activity
#3
Lionel Tarrago, Emmanuel Oheix, Zalán Péterfi, Vadim N Gladyshev
The sulfur-containing amino acid methionine (Met) plays critical roles in protein synthesis, methylation, and sulfur metabolism. Both in its free form and in the form of an amino acid residue, it can be oxidized to the R and S diastereomers of methionine sulfoxide (MetO). Organisms evolved methionine sulfoxide reductases (MSRs) to reduce MetO to Met, with the MSRs type A (MSRA) and type B (MSRB) being specific for the S and R forms of MetO, respectively. In mammals, the selenoprotein MSRB1 plays an important protein repair function, and its expression is tightly regulated by dietary selenium...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916831/the-melanocortin-signaling-camp-axis-accelerates-repair-and-reduces-mutagenesis-of-platinum-induced-dna-damage
#4
Stuart G Jarrett, Katharine M Carter, Brent J Shelton, John A D'Orazio
Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28914943/mammalian-cell-defence-mechanisms-against-the-cytotoxicity-of-nayf4-er-yb-gd-nanoparticles
#5
B Sikora, P Kowalik, J Mikulski, K Fronc, I Kamińska, M Szewczyk, A Konopka, K Zajdel, R Minikayev, K Sobczak, W Zaleszczyk, A Borodziuk, J Rybusiński, J Szczytko, A Sienkiewicz, T Wojciechowski, P Stępień, M Frontczak-Baniewicz, M Łapiński, G Wilczyński, W Paszkowicz, A Twardowski, D Elbaum
Water-soluble upconversion nanoparticles (UCNPs), based on polyvinylpyrrolidone (PVP)-coated NaYF4:Er(3+),Yb(3+),Gd(3+), with various concentrations of Gd(3+) ions and relatively high upconversion efficiencies, were synthesized. The internalization and cytotoxicity of the thus obtained UCNPs were evaluated in three cell lines (HeLa, HEK293 and astrocytes). No cytotoxicity was observed even at concentrations of UCNPs up to 50 μg ml(-1). The fate of the UCNPs within the cells was studied by examining their upconversion emission spectra with confocal microscopy and confirming these observations with transmission electron microscopy...
September 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28912673/improving-the-delivery-of-sod1-antisense-oligonucleotides-to-motor-neurons-using-calcium-phosphate-lipid-nanoparticles
#6
Liyu Chen, Clare Watson, Marco Morsch, Nicholas J Cole, Roger S Chung, Darren N Saunders, Justin J Yerbury, Kara L Vine
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28912086/g-protein-coupled-receptor-kinase-4-induced-cellular-senescence-and-its-senescence-associated-gene-expression-profiling
#7
Pingping Xiao, Xishi Huang, Lanzhen Huang, Jing Yang, Ang Li, Ke Shen, Philip B Wedegaertner, Xiaoshan Jiang
Senescent cells have lost their capacity for proliferation and manifest as irreversibly in cell cycle arrest. Many membrane receptors, including G protein-coupled receptors (GPCRs), initiate a variety of intracellular signaling cascades modulating cell division and potentially play roles in triggering cellular senescence response. GPCR kinases (GRKs) belong to a family of serine/threonine kinases. Although their role in homologous desensitization of activated GPCRs is well established, the involvement of the kinases in cell proliferation is still largely unknown...
September 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28910862/effects-of-newly-synthesized-recombinant-human-amyloid-%C3%AE-complexes-and-poly-amyloid-%C3%AE-fibers-on-cell-apoptosis-and-cognitive-decline
#8
Soojin Park, Jae-Won Huh, Taekil Eom, Naeun Na, Youngjeon Lee, Ju-Sung Kim, Sun-Uk Kim, Insop Shim, Sang-Rae Lee, Ekyune Kim
The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-β peptide (Aβ) in the brain. Aβ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how amyloid beta can be effectively aggregated using prokaryotes and eukaryotes. To express the Aβ42 complex in HEK293 cells, we cloned the Aβ42 region repeatedly and incorporated the resulting construct into a eukaryotic expression vector...
September 15, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28905953/protective-effect-of-potentilla-anserina-polysaccharide-on-cadmium-induced-nephrotoxicity-in-vitro-and-in-vivo
#9
Rong Shen, Disheng Liu, Chenchen Hou, Di Liu, Lixia Zhao, Ju Cheng, Degui Wang, Decheng Bai
The aim of this research was to investigate the antioxidant and anti-apoptotic activities of Potentilla anserina polysaccharide (PAP) on kidney damage induced by cadmium (Cd) in vitro and in vivo. PAP has been suggested to have anti-oxidation, anti-apoptosis, immunoregulation, antimicrobial, antitussive, and expectorant abilities. In this study, PAP was extracted and the major components of PAP were analyzed. It was shown that PAP pretreatment remarkably improved redox homeostasis, both in human embryonic kidney 293 (HEK293) cells and in BALB/c mice...
September 14, 2017: Food & Function
https://www.readbyqxmd.com/read/28904200/epstein-barr-virus-bkrf4-gene-product-is-required-for-efficient-progeny-production
#10
H M Abdullah Al Masud, Takahiro Watanabe, Masahiro Yoshida, Yoshitaka Sato, Fumi Goshima, Hiroshi Kimura, Takayuki Murata
Epstein-Barr virus (EBV), a member of human gammaherpesvirus, infects mainly B cells. EBV has two alternative life cycles, latent and lytic, and is reactivated occasionally from the latent stage to the lytic cycle. To combat EBV-associated disorders, understanding the molecular mechanisms of the EBV lytic replication cycle is also important. Here, we focused on an EBV lytic gene, BKRF4. Using our anti-BKRF4 antibody, we revealed that the BKRF4 gene product is expressed during the lytic cycle with late kinetics...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28895049/mutation-in-gne-downregulates-peroxiredoxin-iv-altering-er-redox-homeostasis
#11
Pratibha Chanana, Gayatri Padhy, Kalpana Bhargava, Ranjana Arya
GNE myopathy is a rare neuromuscular genetic disorder characterized by early adult onset and muscle weakness due to mutation in sialic acid biosynthetic enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). More than 180 different GNE mutations are known all over the world with unclear pathomechanism. Although hyposialylation of glycoproteins is speculated to be the major cause, but cellular mechanism leading to loss of muscle mass has not yet been deciphered. Besides sialic acid biosynthesis, GNE affects other cellular functions such as cell adhesion and apoptosis...
September 11, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28891257/the-k-channel-kzm2-is-involved-in-stomatal-movement-by-modulating-inward-k-currents-in-maize-guard-cells
#12
Yong-Qiang Gao, Wei-Hua Wu, Yi Wang
Stomata are the major gates in plant leaf that allow water and gas exchange, which is essential for plant transpiration and photosynthesis. Stomatal movement is mainly controlled by the ion channels and transporters in guard cells. In Arabidopsis, the inward Shaker K(+) channels, such as KAT1 and KAT2, are responsible for stomatal opening. However, the characterization of inward K(+) channels in maize guard cells is limited. In the present study, we identified two KAT1-like Shaker K(+) channels, KZM2 and KZM3, which were highly expressed in maize guard cells...
September 11, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28890324/direct-head-to-head-evaluation-of-recombinant-adeno-associated-viral-vectors-manufactured-in-human-versus-insect-cells
#13
Oleksandr Kondratov, Damien Marsic, Sean M Crosson, Hector R Mendez-Gomez, Oleksandr Moskalenko, Mario Mietzsch, Regine Heilbronn, Jonathan R Allison, Kari B Green, Mavis Agbandje-McKenna, Sergei Zolotukhin
The major drawback of the Baculovirus/Sf9 system for recombinant adeno-associated viral (rAAV) manufacturing is that most of the Bac-derived rAAV vector serotypes, with few exceptions, demonstrate altered capsid compositions and lower biological potencies. Here, we describe a new insect cell-based production platform utilizing attenuated Kozak sequence and a leaky ribosome scanning to achieve a serotype-specific modulation of AAV capsid proteins stoichiometry. By way of example, rAAV5 and rAAV9 were produced and comprehensively characterized side by side with HEK293-derived vectors...
August 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#14
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
September 6, 2017: Brain Research
https://www.readbyqxmd.com/read/28887287/characterization-of-simvastatin-acid-uptake-by-organic-anion-transporting-polypeptide-3a1-oatp3a1-and-influence-of-drug-drug-interaction
#15
Amandla Atilano-Roque, Melanie S Joy
Human organic anion transporting polypeptide 3A1 (OATP3A1) is predominately expressed in the heart. The ability of OATP3A1 to transport statins into cardiomyocytes is unknown, although other OATPs are known to mediate the uptake of statin drugs in liver. The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene. Treatment with simvastatin acid reduced indoxyl sulfate-mediated reactive oxygen species and modulated OATP3A1 expression in cardiomyocytes and HEK293 cells transfected with the OATP3A1 gene...
September 6, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28885828/multidrug-resistance-protein-4-mrp4-abcc4-protects-cells-from-the-toxic-effects-of-halobenzoquinones
#16
Jinhua Li, Madlen Bauer, Birget Moe, Elaine M Leslie, Xing-Fang Li
Halobenzoquinones (HBQs) are frequently detected disinfection byproducts (DBPs) in treated water. Recent studies have demonstrated that HBQs are highly cytotoxic and capable of inducing the generation of reactive oxygen species (ROS) and depleting cellular glutathione (GSH). Multidrug resistance proteins (MRPs/ABCCs) are known to play a critical role in the elimination of numerous drugs, carcinogens, toxicants, and their conjugated metabolites. In general, little is known about the roles of transporters in DBP toxicity...
September 8, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28883758/hydroquinone-suppresses-ifn-%C3%AE-expression-by-targeting-akt-irf3-pathway
#17
Yong Kim, Han Gyung Kim, Sang Yun Han, Deok Jeong, Woo Seok Yang, Jung-Il Kim, Ji Hye Kim, Young-Su Yi, Jae Youl Cho
Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon (IFN)-β mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK-binding kinase 1 (TBK1)...
September 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28883402/in-search-of-a-small-molecule-agonist-of-the-relaxin-receptor-rxfp1-for-the-treatment-of-liver-fibrosis
#18
Andrew McBride, Anna M Hoy, Mark J Bamford, Danuta E Mossakowska, Martin P Ruediger, Jeremy Griggs, Sapna Desai, Kate Simpson, Ivan Caballero-Hernandez, John P Iredale, Theresa Pell, Rebecca L Aucott, Duncan S Holmes, Scott P Webster, Jonathan A Fallowfield
The peptide hormone human relaxin-2 (H2-RLX) has emerged as a potential therapy for cardiovascular and fibrotic diseases, but its short in vivo half-life is an obstacle to long-term administration. The discovery of ML290 demonstrated that it is possible to identify small molecule agonists of the cognate G-protein coupled receptor for H2-RLX (relaxin family peptide receptor-1 (RXFP1)). In our efforts to generate a new medicine for liver fibrosis, we sought to identify improved small molecule functional mimetics of H2-RLX with selective, full agonist or positive allosteric modulator activity against RXFP1...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883043/ffar2-ffar3-receptor-heteromerization-modulates-short-chain-fatty-acid-sensing
#19
Zhiwei Ang, Ding Xiong, Min Wu, Jeak Ling Ding
Free fatty acid receptors (FFAR2/FFA2/GPR43 and FFAR3/FFA3/GPR41) are mammalian receptors for gut microbiota-derived short-chain fatty acids (SCFAs). These receptors are promising drug targets for obesity, colitis, colon cancer, asthma, and arthritis. Here, we demonstrate that FFAR2 and FFAR3 interact to form a heteromer in primary human monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28882894/zinc-oxide-nanoparticles-provide-anti-cholera-activity-by-disrupting-the-interaction-of-cholera-toxin-with-the-human-gm1-receptor
#20
Shamila Sarwar, Asif Ali, Mahadeb Pal, Pinak Chakrabarti
Vibrio cholerae causes cholera and is the leading cause of diarrhea in the developing countries, highlighting the need for the development of new treatment strategies to combat this disease agent. While exploring the possibility of using zinc oxide (ZnO) nanoparticles (NPs) in cholera treatment, we previously found that ZnO NPs reduce fluid accumulation in mouse ileum induced by the cholera toxin (CT) protein. To uncover the mechanism of action of ZnO NPs on CT activity, here we used classical (O395) and El Tor (C6706) V...
September 7, 2017: Journal of Biological Chemistry
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