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https://www.readbyqxmd.com/read/28717168/dynamics-and-function-of-cxcr4-in-formation-of-the-granule-cell-layer-during-hippocampal-development
#1
Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708385/chloroquine-modified-hydroxyethyl-starch-as-a-polymeric-drug-for-cancer-therapy
#2
Richard Sleightholm, Bin Yang, Fei Yu, Ying Xie, David Oupický
Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. Atomic force microscopy was used to demonstrate a pH-dependent assembly of CQ-HES into well-defined nanoparticles...
July 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28687334/a-cysteine-protease-cathepsin-z-from-disk-abalone-haliotis-discus-discus-genomic-characterization-and-transcriptional-profiling-during-bacterial-infections
#3
G I Godahewa, N C N Perera, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28644509/comparative-transcriptomic-analysis-of-two-important-life-stages-of-angiostrongylus-cantonensis-fifth-stage-larvae-and-female-adults
#4
Liang Yu, Binbin Cao, Ying Long, Meks Tukayo, Chonglv Feng, Wenzhen Fang, Damin Luo
The mechanisms involved in the fast growth of Angiostrongylus cantonensis from fifth-stage larvae (L5) to female adults and how L5 breaks through the blood-brain barrier in a permissive host remain unclear. In this work, we compared the transcriptomes of these two life stages to identify the main factors involved in the rapid growth and transition to adulthood. RNA samples from the two stages were sequenced and assembled de novo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of 1,346 differentially expressed genes between L5 and female adults was then undertaken...
April 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#5
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28610928/kinetic-and-biophysical-characterization-of-a-lysosomal-%C3%AE-l-fucosidase-from-the-fresh-water-mussel-lamellidens-corrianus
#6
A Venugopal, C Sudheer Kumar, Nadimpalli Siva Kumar, Musti J Swamy
Kinetic and biophysical studies have been carried out on a lysosomal α-l-fucosidase purified from the fresh water mussel, Lamellidens corrianus. The enzyme migrates as a single band in SDS-PAGE as well as native PAGE corresponding to a Mr of 56kDa. Mass spectrometric analysis yielded a molecular mass of 56175.1Da for the enzyme, and peptide mass fingerprinting studies showed that it shares sequence homology with other fucosidases. Zymogram analysis showed that the α-l-fucosidase hydrolyzed 4-methyl umbelliferyl α-l-fucopyranoside...
June 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28599312/cullin-3spop-ubiquitin-e3-ligase-promotes-the-poly-ubiquitination-and-degradation-of-hdac6
#7
Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Fei Wu, Jianping Guo, Deliang Liu, Brian J North, Jirong Huo, Jinfang Zhang
The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548682/arthrotomy-based-pre-clinical-models-of-particle-induced-osteolysis-a-systematic-review
#8
REVIEW
Meghan M Moran, Brittany M Wilson, Ryan D Ross, Amarjit S Virdi, D Rick Sumner
We completed a systematic literature review of in vivo animal models that use arthrotomy-based methods to study particle-induced peri-implant osteolysis. The purpose of the review was to characterize the models developed to date, to determine the questions addressed, to assess scientific rigor and transparency and to identify gaps in knowledge. We probed three literature databases (Medline, Embase and Scopus) and found 77 manuscripts that fit the search parameters. In the most recent 10 years, researchers mainly used rat and mouse models, whereas in the previous 20 years large animal, canine and rabbit models were more common...
May 26, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28534963/n-acetylglucosaminyltransferase-iva-promotes-invasion-of-choriocarcinoma
#9
Kimihiro Nishino, Eiko Yamamoto, Kaoru Niimi, Yoko Sekiya, Yoriko Yamashita, Fumitaka Kikkawa
Gestational trophoblastic neoplasia (GTN) results from the malignant transformation of placental trophoblasts which secrete human chorionic gonadotropin (hCG) as do normal placenta or hydatidiform mole. N-acetylglucosaminyltransferase IV (GnT-IV) is a glycosyltransferase which catalyses the formation of β1,4GlcNAc branches on the mannose core of N-glycans. Previous studies reported that β1,4GlcNAc branches on hCG were detected in GTN but not in normal pregnancy or hydatidiform mole. The aim of the present study was to understand the role of GnT-IVa in choriocarcinoma and find the target proteins for GnT-IVa glycosylation which contribute to the malignancy of choriocarcinoma...
May 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28521610/sphk1-sphingosine-kinase-1-induces-epithelial-mesenchymal-transition-by-promoting-the-autophagy-linked-lysosomal-degradation-of-cdh1-e-cadherin-in-hepatoma-cells
#10
Hong Liu, Yan Ma, Hong-Wei He, Wu-Li Zhao, Rong-Guang Shao
SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28486971/a-role-for-cathepsin-z-in-neuroinflammation-provides-mechanistic-support-for-an-epigenetic-risk-factor-in-multiple-sclerosis
#11
Euan R O Allan, Rhiannon I Campden, Benjamin W Ewanchuk, Pankaj Tailor, Dale R Balce, Neil T McKenna, Catherine J Greene, Amy L Warren, Thomas Reinheckel, Robin M Yates
BACKGROUND: Hypomethylation of the cathepsin Z locus has been proposed as an epigenetic risk factor for multiple sclerosis (MS). Cathepsin Z is a unique lysosomal cysteine cathepsin expressed primarily by antigen presenting cells. While cathepsin Z expression has been associated with neuroinflammatory disorders, a role for cathepsin Z in mediating neuroinflammation has not been previously established. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in both wildtype mice and mice deficient in cathepsin Z...
May 10, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28471261/rab17-mediates-intermixing-of-phagocytosed-apoptotic-cells-with-recycling-endosomes
#12
Charles Yin, Dean Argintaru, Bryan Heit
Efferocytosis-the phagocytic removal of apoptotic cells-is required for preventing the presentation of apoptotic cell-derived antigens. This process is regulated by Rab17-dependent sorting of efferocytosed cargos from the phagolysosome to recycling endosomes. In this study we demonstrate that Rab17 is rapidly recruited to efferosomes, followed by migration of the efferosome to the cell center where it intermixes with lysosomes and undergoes Rab17-dependent vesiculation. These efferosome-derived vesicles then traffic in a Rab17-dependent manner to the cell periphery, where they transfer cargo to recycling endosomes...
May 4, 2017: Small GTPases
https://www.readbyqxmd.com/read/28457591/from-mucolipidosis-type-iv-to-ebola-trpml-and-two-pore-channels-at-the-crossroads-of-endo-lysosomal-trafficking-and-disease
#13
REVIEW
Christian Grimm, Elisabeth Butz, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
What do lysosomal storage disorders such as mucolipidosis type IV have in common with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL-cholesterol, certain bacterial toxins and viruses, growth factors, receptors, integrins, macromolecules destined for degradation or secretion are all sorted and transported via the endolysosomal system (ES). There are several pathways known in the ES, e.g. the degradation, the recycling, or the retrograde trafficking pathway. The ES comprises early and late endosomes, lysosomes and recycling endosomes as well as autophagosomes and lysosome related organelles...
April 23, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28456988/gelatin-zymography-using-leupeptin-for-the-detection-of-various-cathepsin-l-forms
#14
Yoko Hashimoto
Zymography is a highly sensitive method to assess the activities as well as molecular weights of enzymes in crude biological fluids and tissue extracts. Cathepsin L is a lysosomal cysteine proteinase that is optimally active at slightly acidic pH and is highly unstable in alkaline solutions such as electrode buffer (pH 8.3). Large amounts of cathepsin L are secreted by various cancer cells, where it promotes invasion and metastasis. Leupeptin is a tight-binding inhibitor of cysteine proteinases, and its complex with cathepsin L is stable in alkaline solutions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28447987/live-cell-imaging-and-3d-analysis-of-angiotensin-receptor-type-1a-trafficking-in-transfected-human-embryonic-kidney-cells-using-confocal-microscopy
#15
Parnika Kadam, Ryan McAllister, Jeffrey S Urbach, Kathryn Sandberg, Susette C Mueller
Live-cell imaging is used to simultaneously capture time-lapse images of angiotensin type 1a receptors (AT1aR) and intracellular compartments in transfected human embryonic kidney-293 (HEK) cells following stimulation with angiotensin II (Ang II). HEK cells are transiently transfected with plasmid DNA containing AT1aR tagged with enhanced green fluorescent protein (EGFP). Lysosomes are identified with a red fluorescent dye. Live-cell images are captured on a laser scanning confocal microscope after Ang II stimulation and analyzed by software in three dimensions (3D, voxels) over time...
March 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28415797/rab7-gtpase-controls-lipid-metabolic-signaling-in-myeloid-derived-suppressor-cells
#16
Xinchun Ding, Wenjing Zhang, Ting Zhao, Cong Yan, Hong Du
Lysosomal acid lipase (LAL) is a critical neutral lipid metabolic enzyme that regulates metabolic reprogramming in myeloid-derived suppressor cells (MDSCs) through over-activation of mammalian target of rapamycin (mTOR). Affymetrix GeneChip microarray analysis of MDSCs from LAL deficient mouse (lal-/-) revealed upregulation of Rab7 GTPase protein, which belongs to a superfamily of small-molecular-weight GTPase known to regulate intracellular membrane trafficking from early to late endosomes and lysosomes. Here, the physical protein-protein interaction between Rab7 GTPase and mTOR has been detected by co-immunoprecipitation in the cell extract of wild type HD1A and lal-/- MDSC-like HD1B myeloid cell lines...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28383524/cytosolic-co-delivery-of-mirna-34a-and-docetaxel-with-core-shell-nanocarriers-via-caveolae-mediated-pathway-for-the-treatment-of-metastatic-breast-cancer
#17
Li Zhang, Xin Yang, Yaqi Lv, Xiaofei Xin, Chao Qin, Xiaopeng Han, Lei Yang, Wei He, Lifang Yin
Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.9 nm, and they efficiently protected miRNA-34a from degradation by RNase and serum...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298487/tgf-%C3%AE-triggers-rapid-fibrillogenesis-via-a-novel-t%C3%AE-rii-dependent-fibronectin-trafficking-mechanism
#18
Archana Varadaraj, Laura M Jenkins, Priyanka Singh, Anindya Chanda, John Snider, N Y Lee, Ayelet R Amsalem-Zafran, Marcelo Ehrlich, Yoav I Henis, Karthikeyan Mythreye
Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β-induced cell migration...
May 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28270132/effects-of-the-lysosomal-destabilizing-drug-siramesine-on-glioblastoma-in-vitro-and-in-vivo
#19
Stine S Jensen, Stine A Petterson, Bo Halle, Charlotte Aaberg-Jessen, Bjarne W Kristensen
BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas...
March 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28248633/evaluation-of-smartflare-probe-applicability-for-verification-of-rnas-in-early-equine-conceptuses-equine-dermal-fibroblast-cells-and-trophoblastic-vesicles
#20
S Budik, W Tschulenk, S Kummer, I Walter, C Aurich
Live cell RNA imaging has become an important tool for studying RNA localisation, dynamics and regulation in cultured cells. Limited information is available using these methods in more complex biological systems, such as conceptuses at different developmental stages. So far most of the approaches rely on microinjection of synthetic constructs into oocytes during or before fertilisation. Recently, a new generation of RNA-specific probes has been developed, the so named SmartFlare probes (Merck Millipore). These consist of a central 15-nm gold particle with target-specific DNAs immobilised on its surface...
March 2, 2017: Reproduction, Fertility, and Development
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