Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry

Glycobiology
Kimberly M AlongeMiklos Guttman

Abstract

Chondroitin sulfates (CS) are long, negatively charged, unbranched glycosaminoglycan (GAG) chains attached to CS-proteoglycan (CSPG) core proteins that comprise the glycan component in both loose interstitial extracellular matrices (ECMs) and in rigid, structured perineuronal net (PNN) scaffolds within the brain. As aberrant CS-PNN formations have been linked to a range of pathological states, including Alzheimer's disease (AD) and schizophrenia, the analysis of CS-GAGs in brain tissue at the disaccharide level has great potential to enhance disease diagnosis and prognosis. Two mass-spectrometry (MS)-based approaches were adapted to detect CS disaccharides from minute fixed tissue samples with low picomolar sensitivity and high reproducibility. The first approach employed a straightforward, quantitative direct infusion (DI)-tandem mass spectrometry (MS/MS) technique to determine the percentages of Δ4S- and Δ6S-CS disaccharides within the 4S/6S-CS ratio, while the second used a comprehensive liquid chromatography (LC)-MS/MS technique to determine the relative percentages of Δ0S-, Δ4S-, Δ6S-, Δ4S6S-CS and Δ2S6S-CS disaccharides, with internal validation by full chondroitin lyase activity. The quantitative accuracy of the five pri...Continue Reading

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Citations

Dec 12, 2020·Experimental Biology and Medicine·Aric F LogsdonMichelle A Erickson
Dec 23, 2020·Journal of the American Society for Mass Spectrometry·Abhigya MookherjeeMiklos Guttman
Sep 6, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Aric F LogsdonKimberly M Alonge
Oct 6, 2021·Mass Spectrometry Reviews·Andreas ZappeKevin Pagel

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