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Heparanase

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https://www.readbyqxmd.com/read/28927006/emerging-roles-of-heparanase-in-viral-pathogenesis
#1
REVIEW
Neel Thakkar, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla
Heparan sulfate (HS) is ubiquitously expressed on mammalian cells. It is a polysaccharide that binds growth factors, cytokines, and chemokines, and thereby controls several important physiological functions. Ironically, many human pathogens including viruses interact with it for adherence to host cells. HS functions can be regulated by selective modifications and/or selective cleavage of the sugar chains from the cell surface. In mammals, heparanase (HPSE) is the only known enzyme capable of regulating HS functions via a selective endoglycosidase activity that cleaves polymeric HS chains at internal sites...
September 18, 2017: Pathogens
https://www.readbyqxmd.com/read/28919014/regulation-and-function-of-endothelial-glycocalyx-layer-in-vascular-diseases
#2
REVIEW
Irina Sieve, Anja Münster-Kühnel, Denise Hilfiker-Kleiner
In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i...
September 12, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28916201/targeting-heparanase-to-the-mammary-epithelium-enhances-mammary-gland-development-and-promotes-tumor-growth-and-metastasis
#3
Ilanit Boyango, Uri Barash, Liat Fux, Inna Naroditsky, Neta Ilan, Israel Vlodavsky
Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor...
September 12, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28888912/chemotherapy-induces-secretion-of-exosomes-loaded-with-heparanase-that-degrades-extracellular-matrix-and-impacts-tumor-and-host-cell-behavior
#4
Shyam K Bandari, Anurag Purushothaman, Vishnu C Ramani, Garrett J Brinkley, Darshan S Chandrashekar, Sooryanarayana Varambally, James A Mobley, Yi Zhang, Elizabeth E Brown, Israel Vlodavsky, Ralph D Sanderson
The heparan sulfate-degrading enzyme heparanase promotes the progression of many cancers by driving tumor cell proliferation, metastasis and angiogenesis. Heparanase accomplishes this via multiple mechanisms including its recently described effect on enhancing biogenesis of tumor exosomes. Because we recently discovered that heparanase expression is upregulated in myeloma cells that survive chemotherapy, we were prompted to investigate the impact of anti-myeloma drugs on exosome biogenesis. When myeloma cells were exposed to the commonly utilized anti-myeloma drugs bortezomib, carfilzomib or melphalan, exosome secretion by the cells was dramatically enhanced...
September 6, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28877607/levels-of-matrix-degrading-enzymes-and-lubricin-in-patients-with-degenerative-joint-disease-requiring-arthroplasty
#5
Christopher Wanderling, Jeffrey Liles, Elissa Davis, Daniel Schmitt, Stephen Statz, Nil Guler, Debra Hoppensteadt, Jawed Fareed, William Hopkinson
Total joint arthroplasty (TJA) of the hip or knee (THA and TKA) is the primary surgical intervention for individuals with degenerative joint disease (DJD). Although it is commonly thought that shear force on the joint causes the degradation of articular cartilage, it is possible that there are other factors that contribute to the progression of DJD. It is plausible that specific enzymes that degrade the joint are upregulated, or conversely, there is downregulation of enzymes critical for joint lubrication. The aim of this study is to profile collagenase-1, elastase, heparanase, and lubricin levels in patients undergoing TJA in order to determine potential preexisting dysregulation that contributes to the pathogenesis of DJD...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28864018/bovine-placentomal-heparanase-and-syndecan-expression-is-related-to-placental-maturation
#6
N Hambruch, S Kumstel, J-D Haeger, C Pfarrer
INTRODUCTION: Impaired placental maturation has been associated with retention of fetal membranes, which is a major reproductive disease in cattle. This maturation includes alterations in all tissue compartments of the placenta, specifically of epithelial and stroma cells and extracellular matrix. It is believed to be controlled by hormones, adhesion molecules and proteolytic enzymes. To investigate if the proteolytic enzyme heparanase and its substrates, the syndecans (SDCs) could be involved in the release of fetal membranes, their expression in bovine placentomes was analyzed...
September 2017: Placenta
https://www.readbyqxmd.com/read/28846389/glycosidase-inhibition-by-multivalent-presentation-of-heparan-sulfate-saccharides-on-bottlebrush-polymers
#7
Eric T Sletten, Ravi S Loka, Fei Yu, Hien M Nguyen
We report herein the first-time exploration of the attachment of well-defined saccharide units onto a synthetic polymer backbone for the inhibition of a glycosidase. More specifically, glycopolymers endowed with heparan sulfate (HS) disaccharides were established to inhibit the glycosidase, heparanase, with an IC50 value in the low nanomolar range (1.05 ± 0.02 nm), a thousand-fold amplification over its monovalent counterpart. The monomeric moieties of these glycopolymers were designed in silico to manipulate the well-established glycotope of heparanase into an inhitope...
September 13, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28837800/systemic-monocyte-chemotactic-protein-1-inhibition-modifies-renal-macrophages-and-restores-glomerular-endothelial-glycocalyx-and-barrier-function-in-diabetic-nephropathy
#8
Margien G S Boels, Angela Koudijs, M Cristina Avramut, Wendy M P J Sol, Gangqi Wang, Annemarie M van Oeveren-Rietdijk, Anton Jan van Zonneveld, Hetty C de Boer, Johan van der Vlag, Cees van Kooten, Dirk Eulberg, Bernard M van den Berg, Daphne H T IJpelaar, Ton J Rabelink
Inhibition of monocyte chemotactic protein-1 (MCP)-1 with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Since the endothelial glycocalyx is also reduced in diabetic nephropathy, we hypothesized that MCP-1 inhibition restores glomerular barrier function through influencing macrophage cathepsin L secretion, thus reducing activation of the glycocalyx degrading enzyme heparanase...
August 21, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28811133/arylamidonaphtalene-sulfonate-compounds-as-a-novel-class-of-heparanase-inhibitors
#9
Riccardo Rondanin, Sara Fochi, Riccardo Baruchello, Tatiana Bernardi, Paola Oliva, Floriana Semeraro, Daniele Simoni, Giuseppe Giannini
The search for antimetastatic agents for cancer therapy may involve the ability of new compounds to maintain the tissue extracellular matrix integrity. Among known factors, heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, is a promising target whose inhibition could represent a strong obstacle for metastatic cancerous mechanisms. The antimetastatic activity of some suramin derivatives reported in literature suggests a possible involvement of the heparanase enzyme. To confirm such hypothesis, we have investigated FCE27266, a molecule known for its antiangiogenic and antimetastatic properties...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28810553/evaluation-of-the-c-domain-of-heparanase-during-age-induced-macrophage-inflammatory-response
#10
Qiaojing Qin, Guang Xu, Weiwei Qi, Mei Guo, Zhaoxia Wang, Wangjie Xu, Zhongdong Qiao, Yong Gu, Jianying Niu
Diabetic vasculopathy is intensified by macrophage inflammation caused by advanced glycation end products (AGEs). Heparanase (HPA) is a unique endoglycosidase, which cleaves heparan sulfate proteoglycans (HSPGs) including syndecan-1 (Syn-1) to further stimulate macrophage cell migration and inflammation. The present study was planned to evaluated the role of C-domain (if any) of HPA in AGE inflammatory response in macrophages. Cell viability was assessed using MTT assay, migration assay, ELISA for tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, mRNA expression by RT-PCR and heparan degrading enzyme assay for HPA activity...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28805269/cloning-and-bacterial-expression-systems-for-recombinant-human-heparanase-production-substrate-specificity-investigation-by-docking-of-a-putative-heparanase-substrate
#11
Angela Pennacchio, Alessandro Capo, Simonetta Caira, Annabella Tramice, Antonio Varriale, Maria Staiano, Sabato D'Auria
Human heparanase (HPSE) is an enzyme that degrades the extracellular matrix. It is implicated in a multiplicity of physiological and pathological processes encouraging angiogenesis and tumor metastasis. The protein is a heterodimer composed from a subunit of 8 kDa and a subunit of 50 kDa. The two protein subunits are non-covalently associated. The cloning and expression of the two protein subunits in Escherichia coli, and their subsequent purification to homogeneity under native conditions result in the production of an active heparanase enzyme...
August 14, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28794202/circhipk3-sponges-mir-558-to-suppress-heparanase-expression-in-bladder-cancer-cells
#12
Yawei Li, Fuxin Zheng, Xingyuan Xiao, Fei Xie, Dan Tao, Chao Huang, Dong Liu, Miao Wang, Liang Wang, Fuqing Zeng, Guosong Jiang
Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively...
September 2017: EMBO Reports
https://www.readbyqxmd.com/read/28766595/design-synthesis-and-evaluation-of-heparan-sulfate-mimicking-glycopolymers-for-inhibiting-heparanase-activity
#13
Ravi S Loka, Fei Yu, Eric T Sletten, Hien M Nguyen
Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics...
August 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28761422/heparan-sulfate-proteoglycans-and-heparanases-in-alzheimer-s-disease-current-outlook-and-potential-therapeutic-targets
#14
Laura Lorente-Gea, Beatriz García, Carla Martín, Luis M Quirós, Iván Fernández-Vega
No abstract text is available yet for this article.
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28743882/hyperoside-pre-treatment-prevents-glomerular-basement-membrane-damage-in-diabetic-nephropathy-by-inhibiting-podocyte-heparanase-expression
#15
Xiaofei An, Lin Zhang, Yanggang Yuan, Bin Wang, Qiuming Yao, Ling Li, Jisheng Zhang, Ming He, Jinan Zhang
Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726915/oleuropein-represses-the-radiation-resistance-of-ovarian-cancer-by-inhibiting-hypoxia-and-microrna-299-targetted-heparanase-expression
#16
Yubai Xing, Dawei Cui, Shun Wang, Pingping Wang, Xiaojing Xing, Hui Li
Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting...
August 1, 2017: Food & Function
https://www.readbyqxmd.com/read/28721300/extracellular-matrix-alterations-in-the-peyronie-s-disease
#17
Marcelo Silva Watanabe, Thérèse Rachel Theodoro, Natália Lima Coelho, Aline Mendes, Monica Luzia Pereira Leonel, Ana Maria Mader, Helena Bonciani Nader, Sidney Glina, Maria Aparecida Silva Pinhal
Peyronie's disease is characterized by fibrous plaque formation of the tunica albuginea, causing penile deformity and fertility problems. The aim of the present study was to investigate alterations in the extracellular matrix in Peyronie's disease. The study used tissues collected by surgical procedure from individuals that presented a well-established disease, while control samples were obtained by biopsies of fresh cadavers. Immunohistochemistry analysis followed by digital quantification was performed to evaluate TGF-β, heparanases and metalloproteinases (MMPs)...
July 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28720149/heparanase-promotes-neuroinflammatory-response-during-subarachnoid-hemorrhage-in-rats
#18
Benjarat Changyaleket, Zhao Zhong Chong, Randal O Dull, Danop Nanegrungsunk, Haoliang Xu
BACKGROUND: Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage. METHODS: Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#19
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
August 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28710312/aspirin-inhibits-cancer-metastasis-and-angiogenesis-via-targeting-heparanase
#20
Xiao-Yang Dai, Juan Yan, Xuhong Fu, Qiuming Pan, Danni Sun, Yuan Xu, Jiang Wang, Litong Nie, Lin-Jiang Tong, Aijun Shen, Mingyue Zheng, Min Huang, Minjia Tan, Hong Liu, Xun Huang, Jian Ding, Meiyu Geng
<br />Recent epidemiological and clinical studies have suggested the benefit of aspirin for cancer patients, which inspired increasing efforts to demonstrate the anti-cancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anti-cancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anti-cancer of aspirin.<br /><br />Experimental Design:<br /><span style="font-size: 11px;">A homogeneous time resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase...
July 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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