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Macropinocytosis

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https://www.readbyqxmd.com/read/28724764/rab5-and-rab11-are-required-for-clathrin-dependent-endocytosis-of-japanese-encephalitis-virus-in-bhk-21-cells
#1
Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen
During infection Japanese Encephalitis Virus generally enters host cells via receptor-mediated clathrin dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and post-internalization of JEV were analyzed using biochemical inhibitors, RNA interference and dominant negative mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol, but not caveolae or macropinocytosis...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28717157/cellular-uptake-pathways-of-sepiolite-nanofibers-and-dna-transfection-improvement
#2
Fidel Antonio Castro-Smirnov, Jeanne Ayache, Jean-Rémi Bertrand, Elodie Dardillac, Eric Le Cam, Olivier Piétrement, Pilar Aranda, Eduardo Ruiz-Hitzky, Bernard S Lopez
Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier because it can be naturally internalized into mammalian cells, due to its nano-size dimension. Therefore, deciphering the mechanisms of sepiolite cell internalization constitutes a question interesting biotechnology, for the use of sepiolite as nanocarrier, as well as environmental and public health concerns. Though it is low, the perfectly stable and natural intrinsic fluorescence of sepiolite nanofibers allows to follow their fate into cells by specifically sensitive technics...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713017/intracellular-co-delivery-of-sr-ion-and-phenamil-drug-through-mesoporous-bioglass-nanocarriers-synergizes-bmp-signaling-and-tissue-mineralization
#3
Jung-Hwan Lee, Nandin Mandakhbayar, Ahmed El-Fiqi, Haw-Won Kim
Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification...
July 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28694083/impact-of-surface-functionalization-on-the-uptake-mechanism-and-toxicity-effects-of-silver-nanoparticles-in-hepg2-cells
#4
Lada Brkić Ahmed, Mirta Milić, Igor M Pongrac, Ana Marija Marjanović, Hrvoje Mlinarić, Ivan Pavičić, Srećko Gajović, Ivana Vinković Vrček
Safe and successful bioapplications of metallic nanoparticles depend on their physicochemical characteristics, in particular their surface properties. This study aimed to investigate how different surface functionalization of silver nanoparticles (AgNP) affect their interaction with mammalian liver cells with regard to cytotoxicity, genotoxicity and mechanism of cellular uptake. Differentially coated AgNP were prepared by surface functionalization using sodium bis(2-ethylhexyl)-sulfosuccinate (AOTAgNP), cetyltrimethylammonium bromide (CTABAgNP), poly(vinylpyrrolidone) (PVPAgNP), poly-l-lysine (PLLAgNP), and bovine serum albumin (BSAAgNP)...
July 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28686970/endocytic-pathways-of-optimized-resveratrol-cubosomes-capturing-into-human-hepatoma-cells
#5
Hend Mohamed Abdel-Bar, Rania Abd El Basset Sanad
Resveratrol (RSV) is a natural polyphenolic compound with high affinity to hepatocytes. It has numerous benefits as anticancer, antioxidant, immunomodulatory and cardioprotective actions. Nevertheless, RSV therapeutic applications are hindered by its low solubility, light sensitivity and extensive first-pass metabolism. Cubosomes are colloidally stable dispersed liquid crystalline nanoparticles. The incorporation of RSV into cubosomes could overcome some of its physicochemical limitations. A Design-Expert(®) software was applied to optimize cubosomes in terms of particle size and encapsulation efficiency (EE%)...
July 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28678485/an-ursolic-acid-derived-small-molecule-triggers-cancer-cell-death-through-hyperstimulation-of-macropinocytosis
#6
Lin Sun, Bin Li, Xiaohui Su, Ge Chen, Yaqin Li, Linqian Yu, Li Li, Wanguo Wei
Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers...
July 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28664153/sopb-mediated-recruitment-of-snx18-facilitates-salmonella-typhimurium-internalization-by-the-host-cell
#7
David Liebl, Xiaying Qi, Yang Zhe, Timothy C Barnett, Rohan D Teasdale
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28663722/bacoside-a-induces-tumor-cell-death-in-human-glioblastoma-cell-lines-through-catastrophic-macropinocytosis
#8
Sebastian John, K C Sivakumar, Rashmi Mishra
Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumor with an extremely poor prognosis. Recent evidences have shown that the "biomechanical imbalances" induced in GBM patient-derived glioblastoma cells (GC) and in vivo via the administration of synthetic small molecules, may effectively inhibit disease progression and prolong survival of GBM animal models. This novel concept associated with de novo anti-GBM drug development has however suffered obstacles in adequate clinical utility due to the appearance of unrelated toxicity in the prolonged therapeutic windows...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28659379/glutamine-fuels-proliferation-but-not-migration-of-endothelial-cells
#9
Boa Kim, Jia Li, Cholsoon Jang, Zoltan Arany
Endothelial metabolism is a key regulator of angiogenesis. Glutamine metabolism in endothelial cells (ECs) has been poorly studied. We used genetic modifications and (13)C tracing approaches to define glutamine metabolism in these cells. Glutamine supplies the majority of carbons in the tricyclic acid (TCA) cycle of ECs and contributes to lipid biosynthesis via reductive carboxylation. EC-specific deletion in mice of glutaminase, the initial enzyme in glutamine catabolism, markedly blunts angiogenesis. In cell culture, glutamine deprivation or inhibition of glutaminase prevents EC proliferation, but does not prevent cell migration, which relies instead on aerobic glycolysis...
June 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28655784/inhibition-of-megakaryocyte-differentiation-by-antibody-drug-conjugates-adcs-is-mediated-by-macropinocytosis-implications-for-adc-induced-thrombocytopenia
#10
Hui Zhao, Sara Gulesserian, Sathish Kumar Ganesan, Jimmy Ou, Karen Morrison, Zhilan Zeng, Veronica Robles, Josh Snyder, Lisa Do, Hector Aviña, Sher Karki, David R Stover, Fernando Doñate
Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and Trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MKs) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers...
June 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28655275/non-transformed-and-cancer-cells-can-utilize-different-endocytic-pathways-to-internalize-dendritic-nanoparticle-variants-implications-on-nanocarrier-design
#11
Nelson K Y Wong, Rajesh A Shenoi, Srinivas Abbina, Irina Chafeeva, Jayachandran N Kizhakkedathu, Mohamed K Khan
Three hyperbranched polyglycerol nanoparticle (HPG NP) variants were synthesized and fluorescently labeled for the study of their cellular interactions. The polymeric nanoparticle that contains a hydrophobic core and a hydrophilic HPG shell, HPG-C10-HPG, is taken up faster by HT-29 cancer cells than non-transformed cells, while similar uptake rates are observed with both cell types for the nanoparticle HPG-C10-PEG that contains a hydrophobic core and a polyethylene glycol shell. The nanoparticle HPG-104, containing neither the hydrophobic core nor the polyethylene glycol shell, is taken up faster by non-transformed cells than HT-29 cells...
June 27, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28651541/the-agglomeration-state-of-nanoparticles-can-influence-the-mechanism-of-their-cellular-internalisation
#12
Blanka Halamoda-Kenzaoui, Mara Ceridono, Patricia Urbán, Alessia Bogni, Jessica Ponti, Sabrina Gioria, Agnieszka Kinsner-Ovaskainen
BACKGROUND: Significant progress of nanotechnology, including in particular biomedical and pharmaceutical applications, has resulted in a high number of studies describing the biological effects of nanomaterials. Moreover, a determination of so-called "critical quality attributes", that is specific physicochemical properties of nanomaterials triggering the observed biological response, has been recognised as crucial for the evaluation and design of novel safe and efficacious therapeutics...
June 26, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28637475/uptake-of-label-free-graphene-oxide-by-caco-2-cells-is-dependent-on-the-cell-differentiation-status
#13
Melanie Kucki, Liliane Diener, Nils Bohmer, Cordula Hirsch, Harald F Krug, Vincenzo Palermo, Peter Wick
BACKGROUND: Understanding the interaction of graphene-related materials (GRM) with human cells is a key to the assessment of their potential risks for human health. There is a knowledge gap regarding the potential uptake of GRM by human intestinal cells after unintended ingestion. Therefore the aim of our study was to investigate the interaction of label-free graphene oxide (GO) with the intestinal cell line Caco-2 in vitro and to shed light on the influence of the cell phenotype given by the differentiation status on cellular uptake behaviour...
June 21, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#14
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28630093/dendritic-cell-sensing-of-hydrophobic-di-and-triacylated-lipopeptides-self-assembled-within-synthetic-virus-like-particles
#15
Rajni Sharma, Arin Ghasparian, John A Robinson, Kenneth C McCullough
Dendritic cells (DCs) play critical roles in developing immune defenses. One important aspect is interaction with pathogen-associated molecular patterns (PAMPs)/danger-associated molecular patterns, including di- and triacylated lipopeptides. Isolated or synthetic lipopeptides are potent vaccine adjuvants, interacting with cell surface TLR2 heterodimers. In contrast, deep embedment within bacteria cell walls would impair lipopeptide interaction with cell surface TLR2, requiring degradation for PAMP recognition...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28627511/fronts-and-waves-of-actin-polymerization-in-a-bistability-based-mechanism-of-circular-dorsal-ruffles
#16
Erik Bernitt, Hans-Günther Döbereiner, Nir S Gov, Arik Yochelis
During macropinocytosis, cells remodel their morphologies for the uptake of extracellular matter. This endocytotic mechanism relies on the collapse and closure of precursory structures, which are propagating actin-based, ring-shaped vertical undulations at the dorsal (top) cell membrane, a.k.a. circular dorsal ruffles (CDRs). As such, CDRs are essential to a range of vital and pathogenic processes alike. Here we show, based on both experimental data and theoretical analysis, that CDRs are propagating fronts of actin polymerization in a bistable system...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28619714/the-g-protein-coupled-receptor-gpr31-promotes-membrane-association-of-kras
#17
Nicole Fehrenbacher, Israel Tojal da Silva, Craig Ramirez, Yong Zhou, Kwang-Jin Cho, Shafi Kuchay, Jie Shi, Susan Thomas, Michele Pagano, John F Hancock, Dafna Bar-Sagi, Mark R Philips
The product of the KRAS oncogene, KRAS4B, promotes tumor growth when associated with the plasma membrane (PM). PM association is mediated, in part, by farnesylation of KRAS4B, but trafficking of nascent KRAS4B to the PM is incompletely understood. We performed a genome-wide screen to identify genes required for KRAS4B membrane association and identified a G protein-coupled receptor, GPR31. GPR31 associated with KRAS4B on cellular membranes in a farnesylation-dependent fashion, and retention of GPR31 on the endoplasmic reticulum inhibited delivery of KRAS4B to the PM...
June 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28607485/exosomes-facilitate-therapeutic-targeting-of-oncogenic-kras-in-pancreatic-cancer
#18
Sushrut Kamerkar, Valerie S LeBleu, Hikaru Sugimoto, Sujuan Yang, Carolina F Ruivo, Sonia A Melo, J Jack Lee, Raghu Kalluri
The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic Kras(G12D), a common mutation in pancreatic cancer...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28596575/infectious-pancreatic-necrosis-virus-enters-chse-214-cells-via-macropinocytosis
#19
Jorge Levican, Camila Miranda-Cárdenas, Ricardo Soto-Rifo, Francisco Aguayo, Aldo Gaggero, Oscar León
Infectious pancreatic necrosis virus (IPNV) is a non-enveloped virus belonging to the Birnaviridae family. IPNV produces an acute disease in salmon fingerlings, with high mortality rates and persistent infection in survivors. Although there are reports of IPNV binding to various cells, the viral receptor and entry pathways remain unknown. The aim of this study was to determine the endocytic pathway that allows for IPNV entry. We observed that IPNV stimulated fluid uptake and virus particles co-localysed with the uptake marker dextran in intracellular compartments, suggesting a role for macropinocytosis in viral entry...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28590839/contractility-differential-tension-and-membrane-removal-lead-zebrafish-epiboly-biomechanics
#20
Maria Marsal, Amayra Hernández-Vega, Enrique Martin-Blanco
Precise tissue remodeling during development is essential for shaping embryos and optimal organ function. Epiboly is an early gastrulation event by which the blastoderm expands around the yolk to engulf it. Three different layers are involved in this process, an epithelial layer (the enveloping layer, EVL), the embryo proper, constituted by the deep cells (DCs), and the yolk cell. Although teleost epiboly has been studied for many years, a clear understanding of its mechanics was still missing. Here we present new information on the cellular, molecular and mechanical elements involved in epiboly that, together with some other recent data and upon comparison with previous biomechanical models, lets conclude that the expansion of the epithelia is passive and driven by active cortical contraction and membrane removal in the adjacent layer, the External Yolk Syncytial Layer (E-YSL)...
June 7, 2017: Cell Cycle
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