Selective inhibition of ventral temporal but not dorsal nasal neurites from mouse retinal explants during contact with chondroitin sulphate

2005 ◽  
Vol 321 (1) ◽  
pp. 9-19 ◽  
Author(s):  
A. W. S. Cheung ◽  
J. S. Y. Lam ◽  
S. O. Chan
Keyword(s):  
Chondroitin Sulphate ◽  
Selective Inhibition ◽  
Retinal Explants

scholarly journals Selective Inhibition of Heparan Sulphate and Not Chondroitin Sulphate by a Small, Soluble Competitive Inhibitor

2021 ◽  
Author(s):  
Marissa L. Maciej-Hulme ◽  
Eamon Dubaissi ◽  
Chun Shao ◽  
Joseph Zaia ◽  
Enrique Amaya ◽  
...  
Keyword(s):  
Small Molecule ◽  
Genetic Manipulation ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Selective Inhibition ◽  
Data Interpretation ◽  
Competitive Inhibitor ◽  
Chain Elongation ◽  
Simple Method ◽  
Chemical Inhibitors

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

scholarly journals Proteoglycan involvement in polyamine uptake

1999 ◽  
Vol 338 (2) ◽  
pp. 317-323 ◽  
Author(s):  
Mattias BELTING ◽  
Susanne PERSSON ◽  
Lars-Åke FRANSSON
Keyword(s):  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Chinese Hamster ◽  
Selective Inhibition ◽  
Lung Fibroblasts ◽  
Ovary Cell ◽  
Wild Type ◽  
Polyamine Biosynthesis ◽  
Heparan Sulphate Proteoglycans ◽  
Mutant Cells

We have evaluated the possible role of proteoglycans in the uptake of spermine by human lung fibroblasts. Exogenous glycosaminoglycans behaved as competitive inhibitors of spermine uptake, the most efficient being heparan sulphate (Ki = 0.16±0.04 µM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-β-d-xylopyranoside or chlorate reduced spermine uptake considerably, whereas chondroitin sulphate lyase had a limited effect. Inhibition of polyamine biosynthesis with α-difluoromethylornithine resulted in an increase of cell-associated heparan sulphate proteoglycans exhibiting higher affinity for spermine. The data indicate a specific role for heparan sulphate proteoglycans in the uptake of spermine by fibroblasts. Spermine uptake by pgsD-677, a mutant Chinese hamster ovary cell defective in heparan sulphate biosynthesis, was only moderately reduced (20%) compared with wild-type cells. Treatment of mutant cells with the above-mentioned xyloside resulted in a greater reduction of endogenous proteoglycan production as well as a higher inhibition of spermine uptake than in wild-type cells. Moreover, treatment with chondroitin sulphate lyase resulted in a selective inhibition of uptake in mutant cells, indicating a role for chondroitin/dermatan sulphate proteoglycans in the uptake of spermine by these cells. Fibroblasts, made growth-dependent on exogenous spermine by α-difluoromethylornithine treatment, were growth-inhibited by heparan sulphate or β-d-xyloside, which might have future therapeutical implications.

scholarly journals Selective Inhibition of Heparan Sulphate and Not Chondroitin Sulphate Biosynthesis by a Small, Soluble Competitive Inhibitor

2021 ◽  
Vol 22 (13) ◽  
pp. 6988
Author(s):  
Marissa L. Maciej-Hulme ◽  
Eamon Dubaissi ◽  
Chun Shao ◽  
Joseph Zaia ◽  
Enrique Amaya ◽  
...  
Keyword(s):  
Small Molecule ◽  
Genetic Manipulation ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Selective Inhibition ◽  
Data Interpretation ◽  
Competitive Inhibitor ◽  
Chain Elongation ◽  
Simple Method ◽  
Chemical Inhibitors

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds provide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole organisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

Stroma-derived factor 1alpha induces a selective inhibition of human erythroid development via the functional upregulation of Fas/CD95 ligand

2000 ◽  
Vol 111 (2) ◽  
pp. 432-440 ◽  
Author(s):  
Davide Gibellini ◽  
Alessandra Bassini ◽  
Maria Carla Re ◽  
Cristina Ponti ◽  
Sebastiano Miscia ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Cd95 Ligand ◽  
Erythroid Development

Increased response preparation overshadows neurophysiological evidence of proactive selective inhibition.

2018 ◽  
Vol 11 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Neil M. Drummond ◽  
Erin K. Cressman ◽  
Anthony N. Carlsen
Keyword(s):  
Selective Inhibition ◽  
Response Preparation

Selective inhibition of chemokine CCL2/MCP-1 reduces experimental pulmonary hypertension

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
D Kosanovic ◽  
BK Dahal ◽  
C Vroom ◽  
E Bieniek ◽  
H Ardeschir Ghofrani ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Selective Inhibition

Healing of Circular Defects in the Rabbit Medial Meniscus Can Occur Spontaneously and Is not Improved by Intra-Articular Hyaluronic Acid

1996 ◽  
Vol 09 (02) ◽  
pp. 60-5 ◽  
Author(s):  
N. Hope ◽  
P. Ghosh ◽  
S. Collier
Keyword(s):  
Hyaluronic Acid ◽  
Medial Meniscus ◽  
Chondroitin Sulphate ◽  
Rabbit Model ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Keratan Sulphate ◽  
Meniscal Healing ◽  
Meniscus Healing ◽  
Made In

SummaryThe aim of this study was to determine the effects of intra-articular hyaluronic acid on meniscal healing. Circular defects, 1.0 mm in diameter, were made in the anterior third of the medial meniscus in rabbits. In one joint, 0.4 ml hyaluronic acid (Healon®) was instilled, and in the contralateral (control) joint, 0.4 ml Ringer’s saline. Four rabbits were killed after four, eight and 12 weeks and the menisci examined histologically. By eight weeks most of the lesions had healed by filling with hyaline-like cartilage. Healing was not improved by hyaluronic acid treatment. The repair tissue stained strongly with alcian blue, and the presence of type II collagen, keratan sulphate, and chondroitin sulphate was demonstrated by immunohistochemical localisation. In contrast to the circular defects, longitudinal incisions made in the medial menisci of a further six rabbits did not show any healing after 12 weeks, indicating that the shape of the lesion largely determined the potential for healing.The effect of hyaluronic acid on meniscal healing was tested in a rabbit model. With one millimeter circular lesions in the medial meniscus, healing by filling with hyalinelike cartilage was not significantly affected by the application of hyaluronic acid intra-articularly at the time of surgery, compared to saline controls, as assessed histologically four, eight and 12 weeks after the operation.

Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

1983 ◽  
Vol 49 (02) ◽  
pp. 096-101 ◽  
Author(s):  
V C Menys ◽  
J A Davies
Keyword(s):  
Arachidonic Acid ◽  
Platelet Adhesion ◽  
Fold Increase ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Selective Inhibitor ◽  
Coated Glass ◽  
Thromboxane Synthetase ◽  
Pre Treatment

SummaryPlatelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated in a rotating probe device by uptake of radio-labelled platelets. Under conditions in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase, reduced platelet adhesion to aortic subendothelium by about 40% but did not affect adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE, a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations of 6-oxo-PGFlα in the perfusate were raised in the presence of dazoxiben alone, and following addition of thrombin (10 units/ml) there was a 2-3 fold increase in concentration. Perfusion of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance of (14C)-labelled-6-oxo-PGFiα. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes detachment of cells from the surface.

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