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Macropinocytosis

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https://www.readbyqxmd.com/read/28920748/investigation-of-the-transport-and-absorption-of-angelica-sinensis-polysaccharide-through-gastrointestinal-tract-both-in-vitro-and-in-vivo
#1
Kaiping Wang, Fang Cheng, Xianglin Pan, Tao Zhou, Xiqiu Liu, Ziming Zheng, Li Luo, Yu Zhang
To investigate the absorption and delivery of ASP in gastrointestinal (GI) tract, cASP was successfully synthesized by chemically modifying with succinic anhydride and then conjugating with a near infrared fluorescent dye Cy5.5. Then, the capacity of oral absorption of cASP was evaluated. The results demonstrated that cASP had low toxicity and no disruption on the integrity of cell membrane. The endocytosis of cASP into the epithelial cells was time- and energy-dependent, which was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28919558/cellular-uptake-of-extracellular-vesicles-is-mediated-by-clathrin-independent-endocytosis-and-macropinocytosis
#2
Helena Costa Verdera, Jerney J Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Recent evidence has established that extracellular vesicles (EVs), including exosomes and microvesicles, form an endogenous transport system through which biomolecules, including proteins and RNA, are exchanged between cells. This endows EVs with immense potential for drug delivery and regenerative medicine applications. Understanding the biology underlying EV-based intercellular transfer of cargo is of great importance for the development of EV-based therapeutics. Here, we sought to characterize the cellular mechanisms involved in EV uptake...
September 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28918901/mtor-inhibition-restores-amino-acid-balance-in-cells-dependent-on-catabolism-of-extracellular-protein
#3
Michel Nofal, Kevin Zhang, Seunghun Han, Joshua D Rabinowitz
Scavenging of extracellular protein via macropinocytosis is an alternative to monomeric amino acid uptake. In pancreatic cancer, macropinocytosis is driven by oncogenic Ras signaling and contributes substantially to amino acid supply. While Ras signaling promotes scavenging, mTOR signaling suppresses it. Here, we present an integrated experimental-computational method that enables quantitative comparison of protein scavenging rates across cell lines and conditions. Using it, we find that, independently of mTORC1, amino acid scarcity induces protein scavenging and that under such conditions the impact of mTOR signaling on protein scavenging rate is minimal...
September 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28917946/cellular-uptake-and-intracellular-localization-of-poly-acrylic-acid-nanoparticles-in-a-rainbow-trout-oncorhynchus-mykiss-gill-epithelial-cell-line-rtgill-w1
#4
Lindsey C Felix, Van A Ortega, Greg G Goss
The ever-growing production of engineered nanoparticles (NPs) for use in many agricultural, commercial, consumer, and industrial applications will lead to their accidental or intentional release into the environment. Potential routes of environmental exposure include manufacturing or transport spills, disposal of NP-containing products down the drain and/or in landfills, as well as direct usage on agricultural land. Therefore, NPs will inevitably contaminate aquatic environments and interact with resident organisms...
September 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28912141/macropinocytosis-of-bevacizumab-by%C3%A2-glioblastoma-cells-in-the-perivascular-niche-affects-their-survival
#5
Gaëlle M Müller-Greven, Cathleen Carlin, Monica E Burgett, Manmeet Singh Ahluwalia, Adam Lauko, Amy S Nowacki, Cameron J Herting, Maha A Qadan, Markus Bredel, Steven A Toms, Justin D Lathia, Dolores Hambardzumyan, Jann N Sarkaria, Petra Hamerlik, Candece L Gladson
PURPOSE: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors. EXPERIMENTAL DESIGN: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133+ cells derived from GBM tumors in vitro...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28901294/pegylated-anticancer-carbon-nanotubes-complex-targeting-mitochondria-of-lung-cancer-cells
#6
Sang-Woo Kim, Yeon Kyung Lee, Jong Yeon Lee, Jeong Hee Hong, Dongwoo Khang
Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated carbon nanotube-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria...
September 13, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28899863/a-unified-approach-to-targeting-the-lysosome-s-degradative-and-growth-signaling-roles
#7
Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murphy, Gordon B Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C Brady, David W Speicher, Jeffrey D Winkler, Ravi K Amaravadi
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e. autophagy and macropinocytosis), while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQs) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy...
September 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28893801/galectin-3-a-druggable-vulnerability-for-kras-addicted-cancers
#8
Laetitia Seguin, Maria F Camargo, Hiromi I Wettersten, Shumei Kato, Jay S Desgrosellier, Tami von Schalscha, Kathryn C Elliott, Erika Cosset, Jacqueline Lesperance, Sara M Weis, David A Cheresh
Identifying the molecular basis for cancer cell dependence on oncogenes such as KRAS can provide new opportunities to target these addictions. Here, we identify a novel role for the carbohydrate-binding protein Galectin-3 as a lynchpin for KRAS dependence. By directly binding to the cell surface receptor integrin αvβ3, Galectin-3 gives rise to KRAS addiction by enabling multiple functions of KRAS in anchorage-independent cells, including formation of macropinosomes that facilitate nutrient uptake and ability to maintain redox balance...
September 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28880029/fluorescence-labelling-of-extracellular-vesicles-using-a-novel-thiol-based-strategy-for-quantitative-analysis-of-cellular-delivery-and-intracellular-traffic
#9
H D Roberts-Dalton, A Cocks, J M Falcon-Perez, E J Sayers, J P Webber, P Watson, A Clayton, A T Jones
Extracellular vesicles, including exosomes, are naturally derived nanovesicles generated in and released by numerous cell types. As extracellular entities they have the capacity to interact with neighbouring cells and distant tissues and affect physiological processes as well as being implicated in numerous diseases including tumorigenesis and neurodegeneration. They are also under intense investigation as delivery vectors for biotherapeutics. The ways in which EVs interact with recipient cells to influence cell physiology and deliver a macromolecular payload are at the early stages of exploration...
September 7, 2017: Nanoscale
https://www.readbyqxmd.com/read/28878781/calreticulin-release-at-an-early-stage-of-death-modulates-the-clearance-by-macrophages-of-apoptotic-cells
#10
Rim Osman, Pascale Tacnet-Delorme, Jean-Philippe Kleman, Arnaud Millet, Philippe Frachet
Calreticulin (CRT) is a well-known "eat-me" signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878355/comparative-study-on-cellular-entry-of-incinerated-ancient-gold-particles-swarna-bhasma-and-chemically-synthesized-gold-particles
#11
Daniel Beaudet, Simona Badilescu, Kiran Kuruvinashetti, Ahmad Sohrabi Kashani, Dilan Jaunky, Sylvie Ouellette, Alisa Piekny, Muthukumaran Packirisamy
Gold nanoparticles (AuNPs) are used for a number of imaging and therapeutic applications in east and western part of the world. For thousands of years, the traditional Indian Ayurvedic approach to healing involves the use of incinerated gold ash, prepared with a variety of plant extracts and minerals depending on the region. Here, we describe the characterization of incinerated gold particles (IAuPs) in HeLa (human cells derived from cervical cancer) and HFF-1 (human foreskin fibroblast cells) in comparison to synthesized citrate-capped gold nanoparticles (AuNPs)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874543/structure-of-the-ebola-virus-envelope-protein-mper-tm-domain-and-its-interaction-with-the-fusion-loop-explains-their-fusion-activity
#12
Jinwoo Lee, David A Nyenhuis, Elizabeth A Nelson, David S Cafiso, Judith M White, Lukas K Tamm
Ebolavirus (EBOV), an enveloped filamentous RNA virus causing severe hemorrhagic fever, enters cells by macropinocytosis and membrane fusion in a late endosomal compartment. Fusion is mediated by the EBOV envelope glycoprotein GP, which consists of subunits GP1 and GP2. GP1 binds to cellular receptors, including Niemann-Pick C1 (NPC1) protein, and GP2 is responsible for low pH-induced membrane fusion. Proteolytic cleavage and NPC1 binding at endosomal pH lead to conformational rearrangements of GP2 that include exposing the hydrophobic fusion loop (FL) for insertion into the cellular target membrane and forming a six-helix bundle structure...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28866775/a-comparative-review-of-viral-entry-and-attachment-during-large-and-giant-dsdna-virus-infections
#13
REVIEW
Haitham Sobhy
Viruses enter host cells via several mechanisms, including endocytosis, macropinocytosis, and phagocytosis. They can also fuse at the plasma membrane and can spread within the host via cell-to-cell fusion or syncytia. The mechanism used by a given viral strain depends on its external topology and proteome and the type of cell being entered. This comparative review discusses the cellular attachment receptors and entry pathways of dsDNA viruses belonging to the families Adenoviridae, Baculoviridae, Herpesviridae and nucleocytoplasmic large DNA viruses (NCLDVs) belonging to the families Ascoviridae, Asfarviridae, Iridoviridae, Phycodnaviridae, and Poxviridae, and giant viruses belonging to the families Mimiviridae and Marseilleviridae as well as the proposed families Pandoraviridae and Pithoviridae...
September 2, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28862080/evaluation-of-brain-targeted-chitosan-nanoparticles-through-blood-brain-barrier-cerebral-microvessel-endothelial-cells
#14
Adem Sahin, Digdem Yoyen-Ermis, Secil Caban-Toktas, Utku Horzum, Yesim Aktas, Patrick Couvreur, Gunes Esendagli, Yilmaz Capan
The blood-brain barrier is the major problem for the treatment of central nervous system diseases. A previous study from our group showed that the brain-targeted chitosan nanoparticles-loaded with large peptide moieties can rapidly cross the barrier and provide neuroprotection. The present study aims to determine the efficacy of the brain-targeted chitosan nanoparticles' uptake by the human blood-brain barrier cerebral microvessel endothelial cells (hCMECs) and to investigate the underlying mechanisms for enhanced cellular entry...
September 1, 2017: Journal of Microencapsulation
https://www.readbyqxmd.com/read/28860768/the-effects-of-collagen-rich-extracellular-matrix-on-the-intracellular-delivery-of-glycol-chitosan-nanoparticles-in-human-lung-fibroblasts
#15
Ji Young Yhee, Hong Yeol Yoon, Hyunjoon Kim, Sangmin Jeon, Polla Hergert, Jintaek Im, Jayanth Panyam, Kwangmeyung Kim, Richard Seonghun Nho
Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28859294/ccaat-enhancer-binding-protein-delta-promotes-intracellular-lipid-accumulation-in-m1-macrophages-of-vascular-lesions
#16
Hong-Yue Lai, Ling-Wei Hsu, Hsin-Hwa Tsai, Yu-Chih Lo, Shang-Hsun Yang, Ping-Yen Liu, Ju-Ming Wang
Aims: Lipid homeostasis is reprogrammed in the presence of inflammation, which results in excessive lipid accumulation in macrophages, and leads to the formation of lipid-laden foam cells. We aimed to link an inflammation-responsive transcription factor CCAAT/enhancer-binding protein delta (CEBPD) with polarized macrophages and dissect its contribution to lipid accumulation. Methods and results: We found that CEBPD protein colocalized with macrophages in human and mouse (C57BL/6, Apoe-/-) atherosclerotic plaques and that Cebpd deficiency in bone marrow cells suppressed atherosclerotic lesions in hyperlipidemic Apoe-/- mice...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28846638/rep1-modulates-autophagy-and-macropinocytosis-to-enhance-cancer-cell-survival
#17
Jungwon Choi, Hyena Kim, Young Ki Bae, Heesun Cheong
Rab escort protein 1 (REP1), a component of the Rab geranyl-geranyltransferase 2 complex, plays a role in Rab protein recruitment in proper vesicles during vesicle trafficking. In addition to having well-known tissue degenerative phenotypes in the REP1 mutant, REP1 is tightly associated with cancer development and contributes to cell growth and survival. However, the functional mechanism of REP1 in cancer progression is largely uninvestigated. Here, we show that REP1 plays a crucial role in regulating mammalian target of rapamycin (mTOR) signaling and its downstream pathways, as well as autophagy and macropinocytosis, which are essential for cancer cell survival during metabolic stresses including starvation...
August 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28831253/endocytotic-uptake-of-hpma-based-polymers-by-different-cancer-cells-impact-of-extracellular-acidosis-and-hypoxia
#18
Daniel Gündel, Mareli Allmeroth, Sarah Reime, Rudolf Zentel, Oliver Thews
BACKGROUND: Polymeric nanoparticles allow to selectively transport chemotherapeutic drugs to the tumor tissue. These nanocarriers have to be taken up into the cells to release the drug. In addition, tumors often show pathological metabolic characteristics (hypoxia and acidosis) which might affect the polymer endocytosis. MATERIALS AND METHODS: Six different N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer structures (homopolymer as well as random and block copolymers with lauryl methacrylate containing hydrophobic side chains) varying in molecular weight and size were analyzed in two different tumor models...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28826499/ingression-type-cell-migration-drives-vegetal-endoderm-internalisation-in-the-xenopus-gastrula
#19
Jason Wh Wen, Rudolf Winklbauer
During amphibian gastrulation, presumptive endoderm is internalised as part of vegetal rotation, a large-scale movement that encompasses the whole vegetal half of the embryo. It has been considered a gastrulation process unique to amphibians, but we show that at the cell level, endoderm internalisation exhibits characteristics reminiscent of bottle cell formation and ingression, known mechanisms of germ layer internalisation. During ingression proper, cells leave a single-layered epithelium. In vegetal rotation, the process occurs in a multilayered cell mass; we refer to it as ingression-type cell migration...
August 10, 2017: ELife
https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#20
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
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