Format

Send to

Choose Destination
Talanta. 2017 Aug 1;170:473-480. doi: 10.1016/j.talanta.2017.04.042. Epub 2017 Apr 19.

Introducing plasma/serum glycodepletion for the targeted proteomics analysis of cytolysis biomarkers.

Author information

1
Université Grenoble-Alpes, F-38000 Grenoble, France; CEA, BIG, Biologie à Grande Echelle, F-38054 Grenoble, France; INSERM, U1038, F-38054 Grenoble, France.
2
INSERM, U1193, Centre Hépatobiliaire, Villejuif F-94800, France; Université Paris Saclay, Faculté de Médecine, Villejuif F-94800, France.
3
INSERM, U1193, Centre Hépatobiliaire, Villejuif F-94800, France; Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Universitaire, Paul Brousse, Villejuif F-94800, France.
4
INSERM, U1193, Centre Hépatobiliaire, Villejuif F-94800, France; Université Paris Saclay, Faculté de Médecine, Villejuif F-94800, France; Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Universitaire, Paul Brousse, Villejuif F-94800, France.
5
Université Grenoble-Alpes, F-38000 Grenoble, France; CEA, BIG, Biologie à Grande Echelle, F-38054 Grenoble, France; INSERM, U1038, F-38054 Grenoble, France. Electronic address: virginie.brun@cea.fr.

Abstract

A major class of clinical biomarkers is constituted of intracellular proteins which are leaking into the blood following ischemia, exposure to toxic xenobiotics or mechanical aggression. Their ectopic presence in plasma/serum is an indicator of tissue damage and raises a warning signal. These proteins, referred to as cytolysis biomarkers, are generally of cytoplasmic origin and as such, are devoid of glycosylation. In contrast, most plasma/serum proteins originate from the hepatic secretory pathway and are heavily glycosylated (at the exception of albumin). Recent advances in targeted proteomics have supported the parallelized evaluation of new blood biomarkers. However, these analytical methods must be combined with prefractionation strategies that reduce the complexity of plasma/serum matrix. In this article, we present the glycodepletion method, which reverses the hydrazide-based glycocapture concept to remove plasma/serum glycoproteins from plasma/serum matrix and facilitates the detection of cytolysis biomarkers. Glycodepletion was integrated to a targeted proteomics pipeline to evaluate 4 liver cytolysis biomarker candidates in the context of acetaminophen-induced acute hepatitis.

KEYWORDS:

Biomarker; Cytolysis; Glycodepletion; Plasma; Protein; Proteomics

PMID:
28501198
DOI:
10.1016/j.talanta.2017.04.042
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center