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Macropinocytosis

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https://www.readbyqxmd.com/read/28323115/gene-transfection-efficiency-into-dendritic-cells-is-influenced-by-the-size-of-cationic-liposomes-dna-complexes
#1
Yoshikazu Inoh, Mie Nagai, Kayo Matsushita, Mamoru Nakanishi, Tadahide Furuno
Cationic liposomes have attracted recent attention as DNA vaccine carriers that can target dendritic cells (DCs). In general, cationic liposome/DNA complexes (lipoplexes) are taken up by various cells via clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis, or phagocytosis, with the mode of endocytosis determining further intracellular trafficking pathways. Moreover, the physicochemical properties of cationic lipoplexes, including lipid composition, shape, size, and charge, influence transfection efficiency, affecting uptake and subsequent intracellular pathways...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28317223/cancer-with-low-cathepsin-d-levels-is-susceptible-to-v-atpase-inhibition
#2
Satoshi Kitazawa, Satoru Nishizawa, Hideyuki Nakagawa, Masaaki Funata, Kazuho Nishimura, Tomoyoshi Soga, Takahito Hara
Vacuolar (H(+) )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anti-cancer drugs has not been realized, possibly owing to their high toxicity in humans. V-ATPase inhibition may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity...
March 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28287688/light-induced-translocation-of-a-conjugated-polyelectrolyte-in-cells-from-fluorescent-probe-to-anticancer-agent
#3
Pan Wu, Naihan Xu, Chunyan Tan, Lei Liu, Ying Tan, Zhifang Chen, Yuyang Jiang
Dual-functional probes, which not only enable visualization of diseased cells but also induce therapeutic cellular responses, are essential to biological studies. In the current work, a conjugated polyelectrolyte, PPET3-N2, was designed and synthesized as a dual-functional probe. The polyphenylene ethynylene terthiophene polymer backbone contributes to the polymer's light-harvesting property to ensure the strong fluorescence as well as photosensitization, whereas quantanary ammonium side chains interact with target organelle for localization...
March 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28276242/cellular-uptake-mechanism-of-cationic-branched-polypeptides-with-poly-l-lys-backbone
#4
Rita Szabó, Mónika Sebestyén, György Kóczán, Ádám Orosz, Gábor Mező, Ferenc Hudecz
Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(Xi)], XiK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Alam)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(Xi-dl-Alam)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Alam-Xi)] (AXK))...
March 9, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28275187/tight-junction-protein-occludin-is-a-porcine-epidemic-diarrhea-virus-entry-factor
#5
Xiaolei Luo, Longjun Guo, Jian Zhang, Yunfei Xu, Weihong Gu, Li Feng, Yue Wang
Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea, has caused huge economic losses in pig-producing countries. Although it was long believed to replicate in the intestinal epithelium using aminopeptidase N as a receptor, the mechanisms of PEDV infection are not fully characterized. In this study, we found that PEDV infection of epithelial cells resulted in the disruption of the tight junctional distribution of occludin to the intracellular localization. Overexpression of occludin in target cells makes them more susceptible for PEDV infection, whereas ablation of occludin expression using siRNA in target cells significantly reduces their susceptibility to virus infection...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250131/measles-virus-enters-breast-and-colon-cancer-cell-lines-through-a-pvrl4-mediated-macropinocytosis-pathway
#6
Sebastien Delpeut, Gary Sisson, Karen M Black, Christopher D Richardson
Measles virus (MeV) is a member of the family Paramixoviridae that causes a highly contagious respiratory disease, but has emerged as a promising oncolytic platform. Previous studies of MeV entry have focused on the identification of cellular receptors. However, the endocytic and trafficking pathways utilized during MeV entry remain poorly described. The contribution of each endocytic pathway has been examined in cells that express MeV receptors, SLAM (Signaling Lymphocyte-Activating Molecule) and PVRL4 (Poliovirus Receptor-Like-4, nectin-4)...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28250113/cxcl12-induced-macropinocytosis-modulates-two-distinct-pathways-to-activate-mtorc1-in-macrophages
#7
Regina Pacitto, Isabella Gaeta, Joel A Swanson, Sei Yoshida
Although growth factors and chemokines elicit different overall effects on cells-growth and chemotaxis, respectively-and activate distinct classes of cell-surface receptors, nonetheless, they trigger similar cellular activities and signaling pathways. The growth factor M-CSF and the chemokine CXCL12 both stimulate the endocytic process of macropinocytosis, and both activate the mechanistic target of rapamycin complex 1 (mTORC1), a protein complex that regulates cell metabolism. Recent studies of signaling by M-CSF in macrophages identified a role for macropinocytosis in the activation of mTORC1, in which delivery of extracellular amino acids into lysosomes via macropinocytosis was required for activation of mTORC1...
March 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28239238/cytokine-imbalance-as-a-common-mechanism-in-both-psoriasis-and-rheumatoid-arthritis
#8
Yong Tan, Qiu Qi, Cheng Lu, Xuyan Niu, Yanping Bai, Chunyan Jiang, Yang Wang, Youwen Zhou, Aiping Lu, Cheng Xiao
Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#9
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
May 2017: Biomaterials
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#10
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28223800/comparison-of-the-cellular-transport-mechanism-of-cationic-star-shaped-polymers-and-liposomes-in-hacat-cells
#11
Heng-Cong Luo, Na Li, Li Yan, Kai-Jin Mai, Kan Sun, Wei Wang, Guo-Juan Lao, Chuan Yang, Li-Ming Zhang, Meng Ren
Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine(®) 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28207819/the-ins-and-outs-of-eukaryotic-viruses-knowledge-base-and-ontology-of-a-viral-infection
#12
Chantal Hulo, Patrick Masson, Edouard de Castro, Andrea H Auchincloss, Rebecca Foulger, Sylvain Poux, Jane Lomax, Lydie Bougueleret, Ioannis Xenarios, Philippe Le Mercier
Viruses are genetically diverse, infect a wide range of tissues and host cells and follow unique processes for replicating themselves. All these processes were investigated and indexed in ViralZone knowledge base. To facilitate standardizing data, a simple ontology of viral life-cycle terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address unique viral replication cycle processes, and existing terminology was modified and adapted. The virus life-cycle is classically described by schematic pictures...
2017: PloS One
https://www.readbyqxmd.com/read/28181394/effects-of-silver-nanoparticles-on-the-interactions-of-neuron-and-glia-like-cells-toxicity-uptake-mechanisms-and-lysosomal-tracking
#13
I-Lun Hsiao, Yi-Kong Hsieh, Chun-Yu Chuang, Chu-Fang Wang, Yuh-Jeen Huang
Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono- and co-culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation...
February 9, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28179028/betanodavirus-like-particles-enter-host-cells-via-clathrin-mediated-endocytosis-in-a-cholesterol-ph-and-cytoskeleton-dependent-manner
#14
Runqing Huang, Guohua Zhu, Jing Zhang, Yuxiong Lai, Yu Xu, Jianguo He, Junfeng Xie
Betanodavirus, also referred to nervous necrosis virus (NNV), is the causative agent of the fatal disease, viral nervous necrosis and has brought significant economic losses in marine and freshwater cultured fish, especially larvae and juveniles. Here, we used an established invasion model with virus-like particle (VLP)-cells, mimicking orange-spotted grouper nervous necrosis virus (OGNNV), to investigate the crucial events of virus entry. VLP were observed in the perinuclear regions of Asian sea bass (SB) cells within 1...
February 8, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28166625/indocyanine-green-labeled-polysarcosine-for-in-vivo-photoacoustic-tumor-imaging
#15
Kohei Sano, Manami Ohashi, Kengo Kanazaki, Akira Makino, Ning Ding, Jun Deguchi, Yuko Kanada, Masahiro Ono, Hideo Saji
Photoacoustic (PA) imaging has been considered an attractive imaging modality for sensitive and in-depth imaging of biomolecules with a high resolution in vivo. PA imaging probes utilizing fluorescence dyes, including indocyanine green (ICG), have been proposed to enhance PA signal intensity. On the other hand, nanomicelles modified with polysarcosine (PSar), a biocompatible hydrophilic polymer, on their surface have previously achieved rapid tumor uptake, suggesting active transport of PSar into tumor tissues...
February 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28156159/cholesterol-peg-comodified-poly-n-butyl-cyanoacrylate-nanoparticles-for-brain-delivery-in-vitro-and-in-vivo-evaluations
#16
Xiao Hu, Feifei Yang, Yonghong Liao, Lin Li, Lan Zhang
This study investigated cholesterol-polyethylene glycol (PEG) comodified poly (ethyleneglycol)-poly (lactide) nanoparticles (CLS-PEG NPs) as a novel, biodegradable brain drug delivery system and included an evaluation of its in vitro and in vivo properties. To this end, coumarin-6 (C6), a fluorescent probe, was encapsulated into CLS-PEG NPs by an emulsion polymerization method. We reported that the use of CLS-PEG NPs led to a sustained drug release in vitro. Additionally, cell viability experiments confirmed their safety...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28150811/size-dependent-cellular-uptake-mechanism-and-cytotoxicity-toward-calcium-oxalate-on-vero-cells
#17
Xin-Yuan Sun, Qiong-Zhi Gan, Jian-Ming Ouyang
Urinary crystals with various sizes are present in healthy individuals and patients with kidney stone; however, the cellular uptake mechanism of calcium oxalate of various sizes has not been elucidated. This study aims to compare the internalization of nano-/micron-sized (50 nm, 100 nm, and 1 μm) calcium oxalate monohydrate (COM) and dihydrate (COD) crystals in African green monkey renal epithelial (Vero) cells. The internalization and adhesion of COM and COD crystals to Vero cells were enhanced with decreasing crystal size...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28145529/intracellular-accumulation-of-gold-nanoparticles-leads-to-inhibition-of-macropinocytosis-to-reduce-the-endoplasmic-reticulum-stress
#18
Nuray Gunduz, Hakan Ceylan, Mustafa O Guler, Ayse B Tekinay
Understanding the toxicity of nanomaterials remains largely limited to acute cellular response, i.e., short-term in vitro cell-death based assays, and analyses of tissue- and organ-level accumulation and clearance patterns in animal models, which have produced very little information about how these materials (from the toxicity point of view) interact with the complex intracellular machinery. In particular, understanding the mechanism of toxicity caused by the gradual accumulation of nanomaterials due to prolonged exposure times is essential yet still continue to be a largely unexplored territory...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28143572/poly-lactic-acid-nanoparticles-pla-np-promote-physiological-modifications-in-lung-epithelial-cells-and-are-internalized-by-clathrin-coated-pits-and-lipid-rafts
#19
Camila Macedo da Luz, Matthew Samuel Powys Boyles, Priscila Falagan-Lotsch, Mariana Rodrigues Pereira, Henrique Rudolf Tutumi, Eidy de Oliveira Santos, Nathalia Balthazar Martins, Martin Himly, Aniela Sommer, Ilse Foissner, Albert Duschl, José Mauro Granjeiro, Paulo Emílio Corrêa Leite
BACKGROUND: Poly-lactic acid nanoparticles (PLA-NP) are a type of polymeric NP, frequently used as nanomedicines, which have advantages over metallic NP such as the ability to maintain therapeutic drug levels for sustained periods of time. Despite PLA-NP being considered biocompatible, data concerning alterations in cellular physiology are scarce. METHODS: We conducted an extensive evaluation of PLA-NP biocompatibility in human lung epithelial A549 cells using high throughput screening and more complex methodologies...
January 31, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28135264/endocytic-reawakening-of-motility-in-jammed-epithelia
#20
Chiara Malinverno, Salvatore Corallino, Fabio Giavazzi, Martin Bergert, Qingsen Li, Marco Leoni, Andrea Disanza, Emanuela Frittoli, Amanda Oldani, Emanuele Martini, Tobias Lendenmann, Gianluca Deflorian, Galina V Beznoussenko, Dimos Poulikakos, Kok Haur Ong, Marina Uroz, Xavier Trepat, Dario Parazzoli, Paolo Maiuri, Weimiao Yu, Aldo Ferrari, Roberto Cerbino, Giorgio Scita
Dynamics of epithelial monolayers has recently been interpreted in terms of a jamming or rigidity transition. How cells control such phase transitions is, however, unknown. Here we show that RAB5A, a key endocytic protein, is sufficient to induce large-scale, coordinated motility over tens of cells, and ballistic motion in otherwise kinetically arrested monolayers. This is linked to increased traction forces and to the extension of cell protrusions, which align with local velocity. Molecularly, impairing endocytosis, macropinocytosis or increasing fluid efflux abrogates RAB5A-induced collective motility...
January 30, 2017: Nature Materials
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