Role of chondroitin sulfates in the projection of vestibular commissures during embryonic hindbrain development

2008 ◽  
Author(s):  
Ying-lai Yuen
Keyword(s):  
Chondroitin Sulfates ◽  
Vestibular Commissures

scholarly journals Epigenetic mechanism of carbohydrate sulfotransferase 3 (CHST3) downregulation in the aging brain

2019 ◽  
Author(s):  
David Baidoe-Ansah ◽  
M Sadman Sakib ◽  
Shaobo Jia ◽  
Andre Fischer ◽  
Rahul Kaushik ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Brain Plasticity ◽  
Epigenetic Mechanism ◽  
Aging Brain ◽  
Chondroitin Sulfates ◽  
Expression Of Genes ◽  
Bona Fide ◽  
Old Mice ◽  
The Brain

AbstractNeural extracellular matrix (ECM) is a complex molecular meshwork surrounding neurons and glial cells in the extracellular space. Structural and functional state of ECM in the brain is tightly regulated by various components of neural ECM such as hyaluronic acid, chondroitin sulfate proteoglycans, link proteins, tenascins, various matrix-modifying enzymes such as chondroitin sulfate synthases and carbohydrate sulfotransferase together with matrix-degrading enzymes. Age-dependent accumulation of ECM molecules is implicated in the age-associated decline in synaptic and cognitive functions. Understanding age-associated changes in the expression of genes involved in regulating various components of ECM can provide an insight into the role of ECM in the aging brain. Hence, in this study, we compared the expression levels of ECM regulating genes in three groups of mice: 2-3 months old mice (2-3M), 22- to 26-month-old mice (22-26M) and more than 30-month-old mice (>30M). Using qPCR, we discovered that in the hippocampus of >30M old mice, the majority of ECM related genes are downregulated, while genes related to neuroinflammation are highly upregulated. This pattern was accompanied by a decrease in cognitive performance of the >30M old mice and was most correlated among ECM-related genes with the downregulation of carbohydrate sulfotransferase 3 (CHST3) gene expression. Interestingly, in 24-26M mice, no general decrease in the expression of ECM related genes was observed, although we still found the upregulation in neuroinflammatory genes and downregulation of CHST3. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region of CHST3 gene in non-neuronal (NeuN-negative) but not in neuronal (NeuN-positive) cells. We conclude that in 22-26 M old brains there are minor changes in expression of the studied bona fide neural ECM genes but there is a prominent epigenetic dysregulation of the CHST3 gene responsible for 6-sulfation of chondroitin sulfates, which may lead to impaired brain plasticity and cognitive decline.

scholarly journals Microbiological-Chemical Sourced Chondroitin Sulfates Protect Neuroblastoma SH-SY5Y Cells against Oxidative Stress and Are Suitable for Hydrogel-Based Controlled Release

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1816
Author(s):  
Emiliano Bedini ◽  
Alfonso Iadonisi ◽  
Chiara Schiraldi ◽  
Laura Colombo ◽  
Diego Albani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuroprotective Effect ◽  
Polymer Networks ◽  
Interpenetrating Polymer Networks ◽  
Ethical Concerns ◽  
Chondroitin Sulfates ◽  
Sulfation Pattern ◽  
Pre Treatment ◽  
Set Up

Chondroitin sulfates (CS) are a class of sulfated glycosaminoglycans involved in many biological processes. Several studies reported their protective effect against neurodegenerative conditions like Alzheimer’s disease. CS are commonly derived from animal sources, but ethical concerns, the risk of contamination with animal proteins, and the difficulty in controlling the sulfation pattern have prompted research towards non-animal sources. Here we exploited two microbiological-chemical sourced CS (i.e., CS-A,C and CS-A,C,K,L) and Carbopol 974P NF/agarose semi-interpenetrating polymer networks (i.e., P.NaOH.0 and P.Ethanol.0) to set up a release system, and tested the neuroprotective role of released CS against H2O2-induced oxidative stress. After assessing that our CS (1–100 µM) require a 3 h pre-treatment for neuroprotection with SH-SY5Y cells, we evaluated whether the autoclave type (i.e., N- or B-type) affects hydrogel viscoelastic properties. We selected B-type autoclaves and repeated the study after loading CS (1 or 0.1 mg CS/0.5 mL gel). After loading 1 mg CS/0.5 mL gel, we evaluated CS release up to 7 days by 1,9-dimethylmethylene blue (DMMB) assay and verified the neuroprotective role of CS-A,C (1 µM) in the supernatants. We observed that CS-A,C exhibits a broader neuroprotective effect than CS-A,C,K,L. Moreover, sulfation pattern affects not only neuroprotection, but also drug release.

scholarly journals Phagocytosis of gelatin-latex particles by a murine macrophage line is dependent on fibronectin and heparin.

1981 ◽  
Vol 90 (1) ◽  
pp. 32-39 ◽  
Author(s):  
L van de Water ◽  
S Schroeder ◽  
E B Crenshaw ◽  
R O Hynes
Keyword(s):  
Dermatan Sulfate ◽  
Keratan Sulfate ◽  
Reticuloendothelial System ◽  
Murine Macrophage ◽  
Temperature Dependent ◽  
Opsonic Activity ◽  
Latex Particles ◽  
Chondroitin Sulfates ◽  
Rapid Assays

It has been suggested that fibronectin plays a role in clearing particles from the circulation by promoting binding to phagocytes of the reticuloendothelial system. By use of a well-defined system to investigate the possible opsonic role of fibronectin, we have studied the uptake of gelatin-coated latex particles by a murine macrophage cell line (P388D1). Fibronectin promotes binding of gelatin-coated beads to these cells in both suspension and monolayer cultures. In both cases there is a requirement for heparin as a cofactor. Other glycosaminoglycans (chondroitin sulfates A and C, dermatan sulfate, and keratan sulfate) were inactive, whereas heparan sulfate was somewhat active. Proof that beads were actually endocytosed was obtained by electron microscopy, which showed beads internalized in membrane-bounded vesicles, and by immunofluorescence analyses, using antibodies to fibronectin to stain external beads. Two rapid assays for the opsonic activity of fibronectin were developed based on differential centrifugation of cell-associated beads and on the immunofluorescence procedure. Binding and endocytosis were time- and temperature-dependent and varied with the amount of gelatin on the beads and with the concentrations of fibronectin and heparin added, and could be inhibited by F(ab')2 antifibronectin. These studies provide a sound basis for a detailed analysis of the interaction of fibronectin with the cell surface and of its involvement in endocytosis.

Visualizing the Molecular and Cellular Basis of Heparin Induced Thrombocytopenia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 228-228
Author(s):  
Lubica Rauova ◽  
Jessica Hirsch ◽  
Teshell Greene ◽  
Chandrasekaran Nagaswami ◽  
Douglas B. Cines ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Thrombus Formation ◽  
Heparin Therapy ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Chondroitin Sulfates ◽  
Activated Platelets ◽  
Visual Evidence ◽  
High Propensity

Abstract Abstract 228 Heparin-induced thrombocytopenia (HIT) is an iatrogenic complication of heparin therapy caused by antibodies that recognize the platelet chemokine, Platelet Factor 4 (PF4), complexed to heparin or to cellular glycosaminoglycans (GAG). The origin of the sentinel feature of HIT - high propensity for thrombosis in the setting of mild thrombocytopenia - remains undefined. We have shown previously that monocytes are particularly susceptible to activation by HIT antibody because unlike platelets, whose surface glycosaminoglycans (GAGs) consist almost entirely of chondroitin sulfates (CS), monocytes express heparan and dermatan sulfates that bind to PF4 with greater affinity. Therefore, antigenic complexes form at lower concentrations of PF4 on monocytes than on platelets and are more resistant to removal by exogenous heparin. We now provide 2 lines of visual evidence in support of this model of the prothrombotic state in HIT: 1) We demonstrate by scanning electron microscopy that spheroidal particles indicative of PF4/GAG complexes are present on the surface of human monocytes upon addition of PF4. 2) Thrombus formation has been visualized in a previously described murine HIT model involving the infusion of the HIT-like monoclonal antibody KKO into mice double-transgenic for human PF4 (hPF4+) and FcγRIIA receptor (FcγRIIA+) on their platelets. After KKO infusion, hPF4+/FcγRIIA+ mice developed vigorous and concurrent accumulation of HIT antigenic complexes and fibrin at sites of laser-induced endothelial injury, not present in similarly treated single transgenic mice. Accumulation of PF4 and fibrin at sites of injury was not increased by a polyclonal anti-hPF4 antibody that does not induce thrombocytopenia in hPF4+/FcγRIIA+ mice. Monocytes and/or monocyte microparticles accumulated at sites of laser-induced injury in KKO-infused hPF4+/FcγRIIA+ mice, but not in KKO-infused single transgenic mice or hPF4+/FcγRIIA+ mice infused with an isotype control, beginning 2.5 min after formation of HIT antigenic complexes and fibrin deposition, accumulating preferentially at the upstream end of developing thrombi. These results provide new insights into the potential role of monocytes in the prothrombotic sequelae of HIT. Antigenic complexes form on monocytes exposed to PF4 and accumulate in HIT antibody-induced thrombi. Monocytes appear to reinforce thrombus formation initiated by injured endothelial cells and activated platelets. Disclosures: Poncz: Diagnostica Stago: Patents & Royalties.

A uronic acid isomerase in Flavobacterium heparinum

1970 ◽  
Vol 48 (2) ◽  
pp. 164-169 ◽  
Author(s):  
James C. Karapally ◽  
Carl P. Dietrich
Keyword(s):  
Hyaluronic Acid ◽  
Equilibrium Point ◽  
Galacturonic Acid ◽  
Uronic Acid ◽  
Glucuronic Acid ◽  
Chondroitin Sulfates ◽  
Isolation And Characterization ◽  
Flavobacterium Heparinum

The isolation and characterization of a uronic acid isomerase from F. heparinum is described. The enzyme converts glucuronic acid and galacturonic acid to fructuronic acid and tagaturonic acid. The equilibrium point of the reaction is affected by buffers. In the presence of borate, 75% of glucuronic acid is converted to fructuronic acid. In the presence of phosphate, the equilibrium is reached when 31% of glucuronic acid is converted to fructuronic acid. Conversely, fructuronic acid and tagaturonic acid are converted to glucuronic acid and galacturonic acid, respectively. Monosaccharides derived from heparin and chondroitin sulfates do not affect the activity of the isomerase, in contrast to the monosaccharides from hyaluronic acid which have marked inhibitory (or diluting) activity upon the enzyme. The role of this enzyme in the metabolism of mucopolysaccharides is discussed.

scholarly journals Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

2002 ◽  
Vol 74 (4) ◽  
pp. 691-716 ◽  
Author(s):  
LENY A. CAVALCANTE ◽  
JOSÉ GARCIA-ABREU ◽  
VIVALDO MOURA NETO ◽  
LUIZ CLAUDIO SILVA ◽  
GILBERTO WEISSMÜLLER
Keyword(s):  
Choice Point ◽  
Axonal Growth ◽  
Eph Receptors ◽  
Chondroitin Sulfates ◽  
Midline Crossing ◽  
The Central Nervous System ◽  
Membrane Bound ◽  
Neuritic Growth ◽  
Cns Midline

Bilaterally symmetric organisms need to exchange information between the left and right sides of their bodies to integrate sensory input and to coordinate motor control. Thus, an important choice point for developing axons is the Central Nervous System (CNS) midline. Crossing of this choice point is influenced by highly conserved, soluble or membrane-bound molecules such as the L1 subfamily, laminin, netrins, slits, semaphorins, Eph-receptors and ephrins, etc. Furthermore, there is much circumstantial evidence for a role of proteoglycans (PGs) or their glycosaminoglycan (GAG) moieties on axonal growth and guidance, most of which was derived from simplified models. A model of intermediate complexity is that of cocultures of young neurons and astroglial carpets (confluent cultures) obtained from medial and lateral sectors of the embryonic rodent midbrain soon after formation of its commissures. Neurite production in these cocultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exerted an inhibitory or non-permissive effect on neuritic growth that was correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment with GAG lyases shows minor effects of CS and discloses a major inhibitory or non-permissive role for HS. The results are discussed in terms of available knowledge on the binding of HSPGs to interative proteins and underscore the importance of understanding glial polysaccharide arrays in addition to its protein complement for a better understanding of neuron-glial interactions.

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