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https://www.readbyqxmd.com/read/27890389/heparanase-confers-a-growth-advantage-to-differentiating-murine-embryonic-stem-cells-and-enhances-oligodendrocyte-formation
#1
Anqi Xiong, Soumi Kundu, Maud Forsberg, Yuyuan Xiong, Tobias Bergström, Tanja Paavilainen, Lena Kjellén, Jin-Ping Li, Karin Forsberg-Nilsson
Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage...
November 23, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#2
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27819680/syndecan-1-increases-b-lymphoid-cell-extravasation-in-response-to-hiv-1-tat-via-%C3%AE-v%C3%AE-3-pp60src-pp125fak-pathway
#3
C Urbinati, E Grillo, P Chiodelli, C Tobia, F Caccuri, S Fiorentini, G David, M Rusnati
Syndecan-1 is a heparan sulfate proteoglycan (HSPG) commonly upregulated in AIDS-related B lymphoid malignancies. Tat is the main HIV-1 transactivating factor that has a major role in the pathogenesis of AIDS-related lymphomas (ARL) by engaging heparan sulfate proteoglycans (HSPGs), chemokine receptors and integrins at the lymphoid cell (LC) surface. Here B-lymphoid Namalwa cell clones that do not express or overexpress syndecan-1 (EV-Ncs and SYN-Ncs, respectively) were compared for their responsiveness with Tat: in the absence of syndecan-1, Tat induces a limited EV-Nc migration via C-X-C motif chemokine receptor 4 (CXCR4), G-proteins and Rac...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27811232/mobility-of-hspg-bound-lpl-explains-how-lpl-is-able-to-reach-gpihbp1-on-capillaries
#4
Christopher M Allan, Mikael Larsson, Rachel S Jung, Michael Ploug, André Bensadoun, Anne P Beigneux, Loren G Fong, Stephen G Young
In mice lacking GPIHBP1, the lipoprotein lipase (LPL) secreted by adipocytes and myocytes remains bound to heparan sulfate proteoglycans (HSPGs) on all cells within tissues. That observation raises a perplexing issue: Why is the freshly secreted LPL in wild-type mice not captured by the same HSPGs, thereby preventing LPL from reaching GPIHBP1 on capillaries. We hypothesized that LPL-HSPG interactions are transient, allowing the LPL to detach and move to GPIHBP1 on capillaries. Indeed, we found that LPL detaches from HSPGs on cultured cells and moves to: (1) soluble GPIHBP1 in the cell culture medium; (2) GPIHBP1-coated agarose beads; and (3) nearby GPIHBP1-expressing cells...
November 3, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27807067/characterization-of-heparan-sulfate-proteoglycan-positive-recycling-endosomes-isolated-from-glioma-cells
#5
Katarzyna A Podyma-Inoue, Takuya Moriwaki, Anupama R Rajapakshe, Kazue Terasawa, Miki Hara-Yokoyama
BACKGROUND: Heparan sulfate proteoglycans (HSPGs)-dependent endocytic events have been involved in glioma progression. Thus, comprehensive understanding of the intracellular trafficking complexes formed in presence of HSPGs would be important for development of glioma treatments. MATERIALS AND METHODS: Subcellular fractionation was used to separate vesicles containing HSPGs from the rat C6 glioma cell line. Isolated HSPG-positive vesicles were further characterized with liquid chromatography-mass spectrometry...
November 2016: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27806323/human-sulfatase-1-exerts-anti-tumor-activity-by-inhibiting-the-akt-cdk4-signaling-pathway-in-melanoma
#6
Xiaoli Lou, Bin Sun, Jianxing Song, Yicun Wang, Junhao Jiang, Yang Xu, Zeqiang Ren, Changqing Su
Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. In most cancers, hSulf-1 is inactivated, which endows cancer cells with increasesed cell proliferation and metastatic activities, inhibition of apoptosis, and decreased sensitivity to radio- and chemotherapy. In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784961/elucidation-of-the-early-infection-machinery-of-hepatitis-b-virus-by-using-bio-nanocapsule
#7
REVIEW
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27693511/infection-of-hepatocytes-with-hcv-increases-cell-surface-levels-of-heparan-sulfate-proteoglycans-uptake-of-cholesterol-and-lipoprotein-and-virus-entry-by-up-regulating-smad6-and-smad7
#8
Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor β signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 30, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27666777/the-heparanase-heparan-sulfate-proteoglycan-axis-a-potential-new-therapeutic-target-in-sarcomas
#9
Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression...
September 22, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27644406/rapid-hepatic-clearance-of-full-length-ccn-2-ctgf-a-putative-role-for-lrp1-mediated-endocytosis
#10
K G F Gerritsen, N Bovenschen, T Q Nguyen, D Sprengers, M P Koeners, A N van Koppen, J A Joles, R Goldschmeding, R J Kok
CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min)...
September 19, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27643669/endothelial-glycocalyx-layer-shedding-following-lung-resection
#11
Alexander Arthur, Phillip J McCall, Lisa Jolly, John Kinsella, Alan Kirk, Ben G Shelley
AIM: We investigated if the serum biomarkers of endothelial glycocalyx layer (EGL) disruption, heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC1) were elevated following lung resection surgery. METHODS: Plasma samples were collected from 16 patients undergoing lobectomy for primary lung cancer. HSPG and SDC1 were measured at five perioperative timepoints. Postoperative oxygenation was recorded. RESULTS: Post-hoc pair wise comparisons showed SDC1 concentration was significantly elevated on postoperative day 2, p < 0...
October 2016: Biomarkers in Medicine
https://www.readbyqxmd.com/read/27589337/the-impact-of-sulfatase-2-on-cancer-progression-and-prognosis-in-patients-with-renal-cell-carcinoma
#12
Shin Kumagai, Kei Ishibashi, Masao Kataoka, Toshiki Oguro, Yuichirou Kiko, Tomohiko Yanagida, Ken Aikawa, Yoshiyuki Kojima
Heparan sulfate-specific endosulfatase-2, SULF-2, can modulate the signaling of HSPG-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCCs) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCCs with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested...
September 2, 2016: Cancer Science
https://www.readbyqxmd.com/read/27580101/tumor-microenvironment-and-angiogenic-blood-vessels-dual-targeting-for-enhanced-anti-glioma-therapy
#13
Quanyin Hu, Ting Kang, Jingxian Feng, Qianqian Zhu, Tianze Jiang, Jianhui Yao, Xinguo Jiang, Jun Chen
Advances in active targeting drug delivery system (DDS) have revolutionized glioma diagnosis and therapy. However, the lack of the sufficient targets on glioma cells and limited penetration capability of DDS have significantly compromised the treatment efficacy. In this study, by taking advantages of the abundant extracellular matrix-derived heparan sulfate proteoglycan (HSPG) and enhanced tumor penetration ability mediated by neuropilin-1 (NRP-1) protein, we reported the ATWLPPR and CGKRK peptide dual-decorated nanoparticulate DDS (designated AC-NP) to achieve angiogenic blood vessels and tumor microenvironment dual-targeting effect...
September 14, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27558418/heparan-sulfate-binding-promotes-accumulation-of-intravitreally-delivered-adeno-associated-viral-vectors-at-the-retina-for-enhanced-transduction-but-weakly-influences-tropism
#14
Kenton T Woodard, Katharine J Liang, William C Bennett, R Jude Samulski
: Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2...
November 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27545211/hemodynamic-shear-stress-regulates-the-transcriptional-expression-of-heparan-sulfate-proteoglycans-in-human-umbilical-vein-endothelial-cell
#15
J-X Liu, Z-P Yan, Y-Y Zhang, J Wu, X-H Liu, Y Zeng
We have previously demonstrated the adaptive remodeling of endothelial glycocalyx under shear stress. However, the underlying mechanism in glycocalyx remodeling, especially the expression of the components heparan sulfate proteoglycans (HSPGs) under shear stress was not completely known. In the present study, we investigated the expression of those HSPGs (syndecan family and glypican-1) in human umbilical vein endothelial cells (HUVECs) responded to the distinct magnitude of shear stress, and performed a systematic and comprehensive analyze on the relationship between shear stress and HSPGs mRNA expression in a temporal manner...
2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27518199/mechanistic-studies-of-viral-entry-an-overview-of-dendrimer-based-microbicides-as-entry-inhibitors-against-both-hiv-and-hsv-2-overlapped-infections
#16
Daniel Sepúlveda-Crespo, Rafael Ceña-Díez, José Luis Jiménez, Ma Ángeles Muñoz-Fernández
This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors...
August 12, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27502167/desulfation-of-cell-surface-hspg-is-an-effective-strategy-for-the-treatment-of-gallbladder-carcinoma
#17
Bin Yi, Yinghe Qiu, Weidan Ji, Miaoyan Wei, Chunying Liu, Zhangxiao Peng, Yongjie Zhang, Zhiwei Quan, Zhaohui Tang, Changqing Su
Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the activation of a variety of cell growth factor signal pathway to promote the progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC specimens and confirmed that the HSPG sulfation level was significantly higher in GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation level was closely associated with poor differentiation, local metastasis, and advanced clinical stage of GBC; it was also associated with the shortening of disease-free survival (DFS) and overall survival (OS) and influenced the outcome of chemotherapy or radio-chemotherapy in patients with GBC recurrence...
October 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27475964/fractones-extracellular-matrix-niche-controlling-stem-cell-fate-and-growth-factor-activity-in-the-brain-in-health-and-disease
#18
Frederic Mercier
The stem cell niche refers to a specific microenvironment where stem cells proliferate and differentiate to produce new specialized cells throughout an organism's adulthood. Growth factors are crucial signaling molecules that diffuse through the extracellular space, reach the stem cell niche, and ultimately promote stem cell proliferation and differentiation. However, it is not well known how multiple growth factors, often with antagonistic activities, work together in the stem cell niche to select target stem cell populations and determine stem cell fate...
July 30, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27400128/apoc-iii-inhibits-clearance-of-triglyceride-rich-lipoproteins-through-ldl-family-receptors
#19
Philip L S M Gordts, Ryan Nock, Ni-Huiping Son, Bastian Ramms, Irene Lew, Jon C Gonzales, Bryan E Thacker, Debapriya Basu, Richard G Lee, Adam E Mullick, Mark J Graham, Ira J Goldberg, Rosanne M Crooke, Joseph L Witztum, Jeffrey D Esko
Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1)...
August 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27321908/a-slow-maturation-process-renders-hepatitis-b-virus-infectious
#20
Stefan Seitz, Caroline Iancu, Tassilo Volz, Walter Mier, Maura Dandri, Stephan Urban, Ralf Bartenschlager
Hepatitis B virus (HBV) replication is strictly limited to the liver. Virions attach to hepatocytes through interactions of the viral PreS envelope protein domain with heparan sulfate proteoglycans (HSPGs). However, HSPG is ubiquitously present on many cell types, suggesting that HBV employs mechanisms to avoid attachment at extrahepatic sites. We demonstrate that HBV particles are released from cells in an inactive form with PreS hidden in the interior. These HSPG-non-binding (N-type) particles develop receptor binding competence by translocating PreS across the envelope onto their surface...
July 13, 2016: Cell Host & Microbe
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