Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography–Tandem Mass Spectrometry

Sun, Xiaojun; Li, Lingyun; Overdier, Katherine H.; Ammons, Lee Anne; Douglas, Ivor S.; Burlew, Clay Cothren; Zhang, Fuming; Schmidt, Eric P.; Chi, Lianli; Linhardt, Robert J.

doi:10.1021/acs.analchem.5b00913

Cited by 83 publications

(100 citation statements)

References 51 publications

(95 reference statements)

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“…Urine glycosaminoglycan content was determined using mass spectrometry, as described in the online supplement (9). Urinary heparanase activity, urinary bikunin, and urinary dimethylmethylene blue (DMMB) were measured as described in the online supplement.…”

Section: Urine Analysesmentioning

confidence: 99%

“…We recently developed a highsensitivity, mass spectrometry-based approach to detect and characterize fragmented GAGs within biologic samples from critically ill patients (9). This highsensitivity approach allows for not only quantification/characterization of HS fragments but also detection of other glycocalyx GAGs, including chondroitin sulfate (CS, a sulfated linear polysaccharide composed of repeating hexuronic acid:N-acetylgalactosamine disaccharides) and hyaluronic acid (HA, an unsulfated linear polysaccharide of repeating glucuronic acid:N-acetylglucosamine disaccharides, Figure 1).…”

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confidence: 99%

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Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome

Schmidt

Overdier²,

Sun³

et al. 2016

Am J Respir Crit Care Med

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129

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Rationale: Degradation of the endothelial glycocalyx, a glycosaminoglycan (GAG)-rich layer lining the vascular lumen, is associated with the onset of kidney injury in animal models of critical illness. It is unclear if similar pathogenic degradation occurs in critically ill patients.Objectives: To determine if urinary indices of GAG fragmentation are associated with outcomes in patients with critical illnesses such as septic shock or acute respiratory distress syndrome (ARDS).Methods: We prospectively collected urine from 30 patients within 24 hours of admission to the Denver Health Medical Intensive Care Unit (ICU) for septic shock. As a nonseptic ICU control, we collected urine from 25 surgical ICU patients admitted for trauma. As a medical ICU validation cohort, we obtained serially collected urine samples from 70 patients with ARDS. We performed mass spectrometry on urine samples to determine GAG (heparan sulfate, chondroitin sulfate, and hyaluronic acid) concentrations as well as patterns of heparan sulfate/chondroitin sulfate disaccharide sulfation. We compared these indices to measurements obtained using dimethylmethylene blue, an inexpensive, colorimetric urinary assay of sulfated GAGs. Measurements and Main Results:In septic shock, indices of GAG fragmentation correlated with both the development of renal dysfunction over the 72 hours after urine collection and with hospital mortality. This association remained after controlling for severity of illness and was similarly observed using the inexpensive dimethylmethylene blue assay. These predictive findings were corroborated using urine samples previously collected at three consecutive time points from patients with ARDS.Conclusions: Early indices of urinary GAG fragmentation predict acute kidney injury and in-hospital mortality in patients with septic shock or ARDS.Clinical trial registered with www.clinicaltrials.gov (NCT01900275).

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Section: Urine Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome

Schmidt

Overdier²,

Sun³

et al. 2016

Am J Respir Crit Care Med

Self Cite

129

145

View full text Add to dashboard Cite

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“…The (GlcA-GlcNAc) 16 -GlcA-pNP chains were further modified by iterative transfer of UDP-GlcNTFA and UDP-GlcA adding five, 9, or 11 additional monosaccharide units. In each case, these chains were capped with either a final GlcNTFA or a GlcNAc residue ( Fig.…”

Section: Top)mentioning

confidence: 99%

“…The online MS analysis was in the multiple reaction monitoring mode. The conditions and collision energies for the all of the disaccharide multiple reaction monitoring transitions were as described before (16).…”

Section: Disaccharide Compositional Analysis Of Precursor and Block Cmentioning

confidence: 99%

Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c

Schultz

Suflita

Liu

et al. 2017

Journal of Biological Chemistry

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A small library of well defined heparan sulfate (HS) polysaccharides was chemoenzymatically synthesized and used for a detailed structure-activity study of fibroblast growth factor (FGF) 1 and FGF2 signaling through FGF receptor (FGFR) 1c. The HS polysaccharide tested contained both undersulfated (NA) domains and highly sulfated (NS) domains as well as very well defined non-reducing termini. This study examines differences in the HS selectivity of the positive canyons of the FGF1 2 -FGFR1c 2 and FGF2 2 -FGFR1c 2 HS binding sites of the symmetric FGF 2 -FGFR 2 -HS 2 signal transduction complex. The results suggest that FGF1 2 -FGFR1c 2 binding site prefers a longer NS domain at the non-reducing terminus than FGF2 2 -FGFR1c 2 . In addition, FGF2 2 -FGFR1c 2 can tolerate an HS chain having an N-acetylglucosamine residue at its non-reducing end. These results clearly demonstrate the different specificity of FGF1 2 -FGFR1c 2 and FGF2 2 -FGFR1c 2 for well defined HS structures and suggest that it is now possible to chemoenzymatically synthesize precise HS polysaccharides that can selectively mediate growth factor signaling. These HS polysaccharides might be useful in both understanding and controlling the growth, proliferation, and differentiation of cells in stem cell therapies, wound healing, and the treatment of cancer.

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“…Options for chromatography steps include hydrophilic liquid interaction, strong anion exchange, and ion-pairing reverse-phase chromatography. Sensitivity can be increased to picomole detection limits by labeling with 2-aminoacridone, allowing analysis of GAG mixtures in biological samples (Yang et al 2012; Sun et al 2015). Liquid chromatography-mass spectrometry techniques can also be used for direct characterization of low molecular weight heparin oligosaccharides (Li et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Heparin and related polysaccharides: synthesis using recombinant enzymes and metabolic engineering

Suflita

et al. 2015

Appl Microbiol Biotechnol

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Glycosaminoglycans are linear anionic polysaccharides that exhibit a number of important biological and pharmacological activities. The two most prominent members of this class of polysaccharides are heparin/heparan sulfate and the chondroitin sulfates (including dermatan sulfate). These polysaccharides, having complex structures and polydispersity, are biosynthesized in the Golgi of most animal cells. The chemical synthesis of these glycosaminoglycans is precluded by their structural complexity. Today, we depend on food animal tissues for their isolation and commercial production. Ton quantities of these glycosaminoglycans are used annually as pharmaceuticals and nutraceuticals. The variability of animal-sourced glycosaminoglycans, their inherent impurities, the limited availability of source tissues, the poor control of these source materials, and their manufacturing processes, suggest a need for new approaches for their production. Over the past decade there have been major efforts in the biotechnological production of these glycosaminoglycans. This mini-review focuses on the use of recombinant enzymes and metabolic engineering for the production of heparin and chondroitin sulfates.

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Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography–Tandem Mass Spectrometry

Cited by 83 publications

References 51 publications

Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome

Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome

Heparan Sulfate Domains Required for Fibroblast Growth Factor 1 and 2 Signaling through Fibroblast Growth Factor Receptor 1c

Heparin and related polysaccharides: synthesis using recombinant enzymes and metabolic engineering

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