The shear-stress sensor function of vascular glycocalyx heparan sulphate and hyaluronic acid was investigated in vivo by assessing flow-mediated dilation before and after their removal. Heparinase III exposure (100 mU·mL for 20 min; = 6) did not significantly affect flow-mediated dilation of the iliac, from 0.42 ± 0.08 mm (mean ± SEM) to 0.34 ± 0.07 mm after ( = 0.12; paired Student's test) for a statistically similar increase in shear stress; 18.24 ± 4.2 N·m for the control and 15.8 ± 3.6 N·m for the heparinase III experiment ( = 0.18). Hyaluronidase exposure (0.14-1.4 mg·mL for 20 min; = 8) also did not significantly reduce flow-mediated dilation of the iliac, which averaged 0.39 ± 0.08 mm before and 0.38 ± 0.09 mm after ( = 0.11) for a statistically similar increase in shear stress; 11.90 ± 3.20 N·m for the control and 9.8 ± 3.33 N·m for the hyaluronidase experiment ( = 0.88). Removal of both heparan sulphate and hyaluronic acid was confirmed using immunohistochemistry. Neither the heparan sulphate nor the hyaluronic acid components of the glycocalyx mediate shear-stress-induced vasodilation in conduit arteries in vivo.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1139/cjpp-2019-0124 | DOI Listing |
Stem Cell Reports
December 2024
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Koch Institute for Integrative Cancer Research at MIT, 500 Main St, Cambridge, MA 02142, USA. Electronic address:
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 hPSCs maintain self-renewal and pluripotency under standard culture conditions that contain high levels of basic fibroblast growth factor(bFGF), a requirement for sufficient bFGF signaling in the engineered cells.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Department of Biochemistry, Center for Biomedical Mass Spectrometry, Boston University School of Medicine, Boston, MA, USA.
Mass spectrometry-based investigation of the heterogeneous glycoproteome from complex biological specimens is a robust approach to mapping the structure, function, and dynamics of the glycome and proteome. Sampling whole wet tissues often provides a large amount of starting material; however, there is a reasonable variability in tissue handling prior to downstream processing steps, and it is difficult to capture all the different biomolecules from a specific region. The on-slide tissue digestion approach, outlined in this protocol chapter, is a simple and cost-effective method that allows comprehensive mapping of the glycoproteome from a single spot of tissue of 1 mm or greater diameter.
View Article and Find Full Text PDFElife
December 2024
Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Introduction: Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.
Methods: We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).
Front Immunol
December 2024
Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Sepsis is a clinical syndrome resulting from the interaction between coagulation, inflammation, immunity and other systems. Coagulation activation is an initial factor for sepsis to develop into multiple organ dysfunction. Therefore, anticoagulant therapy may be beneficial for sepsis patients.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!