A microscopic view on the renal endothelial glycocalyx

Dane, Martijn J. C.; Berg, Bernard M. van den; Lee, Dae Hyun; Boels, Margien G. S.; Tiemeier, Gesa L.; Avramut, M. Cristina; Zonneveld, Anton Jan van; Vlag, Johan van der; Vink, Hans; Rabelink, Ton J.

doi:10.1152/ajprenal.00532.2014

Cited by 107 publications

(76 citation statements)

References 117 publications

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“…The major components of the glycocalyx are GAGs and the thickness of the glycocalyx is 50 to 100 times more than that of the cell membrane phospholipid bilayer [57]. However, the glycocalyx is a highly dynamic and fragile structure ex vivo, traditional tissue processing for staining and perfusion-fixation usually results in a partial or complete loss of the glycocalyx [58]. Moreover, the variable GAG structures are difficult to define compared to that of DNAs, RNAs, and proteins, the roles of glycocalyx and GAGs played in biology and medicine are largely ignored during the past.…”

Section: Discussionmentioning

confidence: 99%

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

Lan

et al. 2017

Cell Physiol Biochem

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Background/Aims: Bleomycin is a clinically used anti-cancer drug that produces DNA breaks once inside of cells. However, bleomycin is a positively charged molecule and cannot get inside of cells by free diffusion. We previously reported that the cell surface negatively charged glycosaminoglycans (GAGs) may be involved in the cellular uptake of bleomycin. We also observed that a class of positively charged small molecules has Golgi localization once inside of the cells. We therefore hypothesized that bleomycin might perturb Golgi-operated GAG biosynthesis. Methods: We used stable isotope labeling coupled with LC/MS analysis of GAG disaccharides simultaneously from bleomycin-treated and non-treated cancer cells. To further understand the cytotoxicity of bleomycin and its relationship to GAGs, we used sodium chlorate to inhibit GAG sulfation and commercially available GAGs to compete for cell surface GAG/bleomycin interactions in seven cell lines including CHO745 defective in both heparan sulfate and chondroitin sulfate biosynthesis. Results: we discovered that heparan sulfate GAG was significantly undersulfated and the quantity and disaccharide compositions of GAGs were changed in bleomycin-treated cells in a concentration- and time-dependent manner. We revealed that bleomycin-induced cytotoxicity was directly related to cell surface GAGs. Conclusion: GAGs were targeted by bleomycin both at cell surface and at Golgi. Thus, GAGs might be the biological relevant molecules that might be related to the bleomycin-induced fibrosis in certain cancer patients, a severe side effect with largely unknown molecular mechanism.

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Section: Discussionmentioning

confidence: 99%

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

Lan

et al. 2017

Cell Physiol Biochem

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“…The net negative charge of the glycocalyx is thought to play a role in the charge selectivity of the GFB, helping restrict the passage of the negatively charged macromolecule, albumin (12). While some data does not support this 'charge selectivity' theory (19), it is likely that the glycocalyx, functioning as a hydrogel, forms a physical barrier that is important for permselectivity (12,20). The development of albuminuria in experimental models of diabetes is associated with changes in the glycocalyx, including loss of GAGs (12), which may occur due to hyperglycemia-induced disruption of GAG synthesis (21).…”

Section: Glomerular Endothelial Cells: Adapted For Selective Permeabimentioning

confidence: 99%

The Players: Cells Involved in Glomerular Disease

Kitching

Hutton

2016

CJASN

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Glomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others. In addition to those cells intrinsic to the glomerulus, leukocytes patrol the glomerulus in health and mediate injury in disease. Distinct leukocyte types and subsets are present, with some being involved in different ways in an individual glomerular disease. Cells of the innate and adaptive immune systems are important, directing systemic immune and inflammatory responses, locally mediating injury, and potentially dampening inflammation and facilitating repair. The advent of new genetic and molecular techniques, and new disease models means that we better understand both the basic biology of the glomerulus and the pathogenesis of glomerular disease. This understanding should lead to better diagnostic techniques, biomarkers, and predictors of prognosis, disease severity, and relapse. With this knowledge comes the promise of better therapies in the future, directed toward halting pathways of injury and fibrosis, or interrupting the underlying pathophysiology of the individual diseases that lead to significant and progressive glomerular disease.

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“…Since endothelial glycocalyx has negative charge, it repels negative particles and binds to cationic dyes. 28,29 Similarly, ocular glycocalyx contains polyanions 30 such as sialylated O-glycans 31,32 that have negative charge. The authors hypothesize that cationic dyes bind to conjunctival glycocalyx while anionic dyes are repelled by glycocalyx.…”

Section: Anionic Dyes Versus Cationic Dyesmentioning

confidence: 99%

“Coffee Ring Effect” in Ophthalmology

Rajabi

Sharifzadeh²

2016

Medicine

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The process of formation of Marx line is studied in this article. Various theories have been proposed previously, in order to explain the mechanisms which lead to the development of Marx line. These theories are based on the characteristics of stained area and do not pay attention to the behavior of dye solution itself on the surface. The aim of this study is to investigate the latter behavior and introduce a new theory based on it, in order to explain the process of the Marx line formation.This study also introduces “Coffee Ring Effect” and its possible applications in explaining some ophthalmological phenomena.The effect of dye solution's behavior on the beneath surface is adopted in order to propose a novel theory. This new hypothesis is called “Anionic Dye Deposition” which was based on “Coffee Ring Effect” phenomenon. For evaluation of this theory, Evaporation pattern of Rose Bengal and fluorescein were analyzed on different surfaces. Furthermore, the effect of tear meniscus alteration on lid margin staining is studied.During the evaporation process of dye solutions, it was observed that almost all of the solute was deposited at the edge of the drop on hydrophilic surfaces. Furthermore, in the study of lid margin staining, it is observed that tear meniscus alteration during gaze affects staining pattern. This observation invalidates former hypotheses which only focus on stained surface characteristics.According to the observations in this study, it is proposed that Marx line staining occurs as a result of “anionic dye deposition” due to evaporation.

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A microscopic view on the renal endothelial glycocalyx

Abstract: Dane MJ, van den Berg BM, Lee DH, Boels MG, Tiemeier GL, Avramut MC, van Zonneveld AJ, van der Vlag J, Vink H, Rabelink TJ. A microscopic view on the renal endothelial glycocalyx.

Cited by 107 publications

References 117 publications

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

Heparan Sulfate and Chondroitin Sulfate Glycosaminoglycans Are Targeted by Bleomycin in Cancer Cells

The Players: Cells Involved in Glomerular Disease

“Coffee Ring Effect” in Ophthalmology

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