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241.
Brooke L. Farrugia John M. Whitelock Robert O’Grady Bruce Caterson Megan S. Lord 《The journal of histochemistry and cytochemistry》2016,64(2):85-98
The granules of mast cells contain a myriad of mediators that are stored and protected by the sulfated glycosaminoglycan (GAG) chains that decorate proteoglycans. Whereas heparin is the GAG predominantly associated with mast cells, mast cell proteoglycans are also decorated with heparan sulfate and chondroitin sulfate (CS). This study investigated a unique CS structure produced by mast cells that was detected with the antibody clone 2B6 in the absence of chondroitinase ABC digestion. Mast cells in rodent tissue sections were characterized using toluidine blue, Leder stain and the presence of mast cell tryptase. The novel CS epitope was identified in rodent tissue sections and localized to cells that were morphologically similar to cells chemically identified as mast cells. The rodent mast cell-like line RBL-2H3 was also shown to express the novel CS epitope. This epitope co-localized with multiple CS proteoglycans in both rodent tissue and RBL-2H3 cultured cells. These findings suggest that the novel CS epitope that decorates mast cell proteoglycans may play a role in the way these chains are structured in mast cells. 相似文献
242.
Dr. Tuba Unver Prof. Dr. Ayse Sebnem Erenler Prof. Dr. Murat Bingul Prof. Dr. Mehmet Boga 《化学与生物多样性》2023,20(10):e202300924
Chondroitin synthesis was performed using the recombinant Escherichia coli(C2987) strain created by transforming the plasmid pETM6-PACF-vgb, which carries the genes responsible for chondroitin synthesis, kfoA, kfoC, kfoF, and the Vitreoscilla hemoglobin gene (vgb). Then, Microbial chondroitin sulfate (MCS)’s antioxidant, anticholinesterase, and antibacterial activity were compared with commercial chondroitin sulfate (CCS). The antioxidant studies revealed that the MCS and CCS samples could be potential targets for scavenging radicals and cupric ion reduction. MCS demonstrated better antioxidant properties in the ABTS assay with the IC50 value of 0.66 mg than CCS. MCS showed 2.5-fold for DPPH and almost 5-fold for ABTS⋅+ (with a value of 3.85 mg/mL) better activity than the CCS. However, the compounds were not active for cholinesterase enzyme inhibitions. In the antibacterial assay, the Minimum inhibitory concentration (MIC) values of MCS against S. aureus, E. aerogenes, E. coli, P. aeruginosa, and K. pneumoniae (0.12, 0.18, 0.12, 0.18, and 0.18 g/mL, respectively) were found to be greater than that of CCS (0.42, 0.48, 0.36, 0.36, and 0.36 g/mL, respectively). This study demonstrates that MCS is a potent pharmacological agent due to its physicochemical properties, and its usability as a therapeutic-preventive agent will shed light on future studies. 相似文献
243.
Hao Wang Lin Zhang Yang Wang Jianghua Li Guocheng Du Zhen Kang 《Biotechnology journal》2021,16(5):2000321
Chondroitinase ABC I (csABC I) has attracted intensive attention because of its great potential in heparin refining and the enzymatic preparation of low-molecular-weight chondroitin sulfate (LMW-CS). However, low thermal resistance (<30℃) restricts its applications. Herein, structure-guided and sequence-assisted combinatorial engineering approaches were applied to improve the thermal resistance of Proteus vulgaris csABC I. By integrating the deletion of the flexible fragment R166–L170 at the N-terminal domain and the mutation of E694P at the C-terminal domain, variant NΔ5/E694P exhibited 247-fold improvement of its half-life at 37℃ and a 2.3-fold increase in the specific activity. Through batch fermentation in a 3-L fermenter, the expression of variant NΔ5/E694P in an Escherichia coli host reached 1.7 g L−1 with the activity of 1.0 × 105 U L−1. Finally, the enzymatic approach for the preparation of LMW-CS was established. By modulating enzyme concentration and controlling depolymerization time, specifically distributed LMW-CS (7000, 3400, and 1900 Da) with low polydispersity was produced, demonstrating the applicability of these processes for the industrial production of LMW-CS in a more environmentally friendly way. 相似文献
244.
245.
Markus Morawski Alexander Dityatev Maike Hartlage-Rübsamen Maren Blosa Max Holzer Katharina Flach Sanja Pavlica Galina Dityateva Jens Grosche Gert Brückner Melitta Schachner 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1654)
Perineuronal nets (PNs) in the brains of tenascin-R-deficient (tn-r−/−) mice develop in temporal concordance with those of wild-type (tn-r+/+) mice. However, the histological appearance of PNs is abnormal in adult tn-r−/− mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r−/− mice and whether the structure of PNs could be normalized. In tn-r−/− cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r+/+ mice. Experiments to normalize the structure of PNs in tn-r−/− organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r+/+ and tn-r−/− brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin Wisteria floribunda agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction. 相似文献
246.
Keiichi Takagaki Kaoru Kojima Mitsuo Majima Toshiya Nakamura Ikunoshin Kato Masahiko Endo 《Glycoconjugate journal》1992,9(4):174-179
Oligosaccharides from hyaluronic acid and chondroitin 6-sulfate were prepared by digestion with testicular hyaluronidase and separated according to their degree of polymerization by gel-permeation chromatography. These materials were successively analyzed by negative-mode ion-spray mass spectrometry with an atmospheric-pressure ion source. An ion-spray interface was used to produce ions via the ion evaporation process, producing mass spectra containing a series of molecular species carrying multiple charges. Using two adjacent multiply charged molecular ions, the exact molecular weights up to the tetradecasaccharide were calculated with a precision of ±1 dalton. This type of mass spectrometry was also demonstrated to be feasible for the analysis of mixtures of oligosaccharides, including tetra-, hexa-, octa- and decasaccharides, from hyaluronic acid or chondroitin 6-sulfate without separation. Ion-spray mass spectrometry was thus shown to be applicable to the structural analysis of oligosaccharides from glycosaminoglycans.Abbreviations HA
hyaluronic acid
- Ch6S
chondroitin 6-sulfate
- GAG
glycosaminoglycan
- GlcA
d-glucuronic acid
- GlcNAc
2-acetamido-2-deoxy-d-glucose
- GalNAc
2-acetamido-2-deoxy-d-galactose. 相似文献
247.
《Journal of molecular biology》2023,435(12):168140
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and its prevalence is increasing with age. A wealth of genetic evidence indicates that the endo-lysosomal system is a major pathway driving PD pathogenesis with a growing number of genes encoding endo-lysosomal proteins identified as risk factors for PD, making it a promising target for therapeutic intervention. However, detailed knowledge and understanding of the molecular mechanisms linking these genes to the disease are available for only a handful of them (e.g. LRRK2, GBA1, VPS35). Taking on the challenge of studying poorly characterized genes and proteins can be daunting, due to the limited availability of tools and knowledge from previous literature. This review aims at providing a valuable source of molecular and cellular insights into the biology of lesser-studied PD-linked endo-lysosomal genes, to help and encourage researchers in filling the knowledge gap around these less popular genetic players. Specific endo-lysosomal pathways discussed range from endocytosis, sorting, and vesicular trafficking to the regulation of membrane lipids of these membrane-bound organelles and the specific enzymatic activities they contain. We also provide perspectives on future challenges that the community needs to tackle and propose approaches to move forward in our understanding of these poorly studied endo-lysosomal genes. This will help harness their potential in designing innovative and efficient treatments to ultimately re-establish neuronal homeostasis in PD but also other diseases involving endo-lysosomal dysfunction. 相似文献
248.
Anna S. Eriksson Dorothe Spillmann 《The journal of histochemistry and cytochemistry》2012,60(12):936-942
Proteoglycans, with their core proteins and attached glycosaminoglycan chains, are
recognized as important partners in many biological processes, yet often experimental
analysis of their molecular action is considered for only part of these molecules: either
the protein or the carbohydrate unit. In this article, we have tried to summarize, with an
example of the syndecan family in general and more specifically with syndecan-1, what is
known considering the mutual influence of these different components, and we follow
whether the nature of the glycosaminoglycan chains matters for these effects. 相似文献
249.
I. I. Ermakova T. A. Chertkova A. L. Mokrushin G. A. Sakuta A. V. Romaniouk V. I. Morozov 《Cell and Tissue Biology》2008,2(5):538-545
Proteoglycans were isolated from the extracellular matrix (ECM) of L6J1 rat myoblasts; their influence on myoblast adhesion has been studied. Proteoglycan digestion with chondroitinase AC and heparinase III, which degrade polysaccharide moieties, has revealed that chondroitin sulfate proteoglycans are a major class of myoblast extracellular matrix proteoglycans. Electrophoresis of enzymatically processed proteoglycans was used to examine their core proteins. Myoblast adhesion was suppressed by proteoglycans or a mixture of proteoglycans and a fibronectin-extracellular matrix. Myoblast adhesion to a substrate composed of fibronectin and proteoglycans is restored after the substrate was treated with chondroitinase AC. In conclusion, proteoglycans of L6J1 rat myoblast ECMs were isolated and purified. Chondroitin sulfate proteoglycans are a major class of proteoglycans. Isolated proteoglycans suppressed myoblast adhesion; the effect was mediated by polysaccharide moieties of proteoglycans. 相似文献
250.
Maria C. Bewley Lovely Gautam Mashanipalya G. Jagadeeshaprasad D. Channe Gowda John M. Flanagan 《The Journal of biological chemistry》2020,295(52):18589
VAR2CSA is the placental-malaria–specific member of the antigenically variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. It is expressed on the surface of Plasmodium falciparum-infected host red blood cells and binds to specific chondroitin-4-sulfate chains of the placental proteoglycan receptor. The functional ∼310 kDa ectodomain of VAR2CSA is a multidomain protein that requires a minimum 12-mer chondroitin-4-sulfate molecule for specific, high affinity receptor binding. However, it is not known how the individual domains are organized and interact to create the receptor-binding surface, limiting efforts to exploit its potential as an effective vaccine or drug target. Using small angle X-ray scattering and single particle reconstruction from negative-stained electron micrographs of the ectodomain and multidomain constructs, we have determined the structural architecture of VAR2CSA. The relative locations of the domains creates two distinct pores that can each accommodate the 12-mer of chondroitin-4-sulfate, suggesting a model for receptor binding. This model has important implications for understanding cytoadherence of infected red blood cells and potentially provides a starting point for developing novel strategies to prevent and/or treat placental malaria. 相似文献