Imperial College London
Alternate

Emeritus Professor Howard R. Morris FRS

Faculty of Natural Sciences, Department of Life Sciences

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 7594 5221h.morris

 
 
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Assistant

 

Miss Cathy Thomas +44 (0)20 7594 5220

 
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Location

 

103Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lee:2011:10.2337/db10-1186,
author = {Lee, C and Chiu, PCN and Pang, P and Chu, IK and Lee, K and Koistinen, R and Koistinen, H and Seppälä, M and Morris, HR and Tissot, B and Panico, M and Dell, A and Yeung, WSB},
doi = {10.2337/db10-1186},
journal = {Diabetes},
pages = {909--917},
title = {Glycosylation Failure Extends to Glycoproteins in Gestational Diabetes Mellitus: Evidence From Reduced α2-6 Sialylation and Impaired Immunomodulatory Activities of Pregnancy-Related Glycodelin-A},
url = {http://dx.doi.org/10.2337/db10-1186},
volume = {60},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVE Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy. Patients with GDM are at risk for high fetal mortality and gestational complications associated with reduced immune tolerance and abnormal carbohydrate metabolism. Glycodelin-A (GdA) is an abundant decidual glycoprotein with glycosylation-dependent immunomodulatory activities. We hypothesized that aberrant carbohydrate metabolism in GDM was associated with changes in glycosylation of GdA, leading to defective immunomodulatory activities.RESEARCH DESIGN AND METHODS GdA in the amniotic fluid from women with normal (NGdA) and GDM (DGdA) pregnancies was purified by affinity chromatography. Structural analysis of protein glycosylation was preformed by lectin-binding assay and mass spectrometry. Cytotoxicity, cell death, cytokine secretion, and GdA binding of the GdA-treated lymphocytes and natural killer (NK) cells were determined. The sialidase activity in the placental tissue from normal and GDM patients was measured.RESULTS GDM affected the glycosylation but not the protein core of GdA. Specifically, DGdA had a lower abundance of α2-6–sialylated and high-mannose glycans and a higher abundance of glycans with Sda (NeuAcα2-3[GalNAcβ1-4]Gal) epitopes compared with NGdA. DGdA had reduced immuosuppressive activities in terms of cytotoxicity on lymphocytes, inhibitory activities on interleukin (IL)-2 secretion by lymphocytes, stimulatory activities on IL-6 secretion by NK cells, and binding to these cells. Desialylation abolished the immunomodulation and binding of NGdA. Placental sialidase activity was increased in GDM patients, which may account for the reduced sialic acid content of DGdA.CONCLUSIONS Taken together, this study provides the first direct evidence for altered enzymatic glycosylation and impaired bioactivity of GdA in GDM patients.
AU  - Lee,C
AU  - Chiu,PCN
AU  - Pang,P
AU  - Chu,IK
AU  - Lee,K
AU  - Koistinen,R
AU  - Koistinen,H
AU  - Seppälä,M
AU  - Morris,HR
AU  - Tissot,B
AU  - Panico,M
AU  - Dell,A
AU  - Yeung,WSB
DO  - 10.2337/db10-1186
EP  - 917
PY  - 2011///
SP  - 909
TI  - Glycosylation Failure Extends to Glycoproteins in Gestational Diabetes Mellitus: Evidence From Reduced α2-6 Sialylation and Impaired Immunomodulatory Activities of Pregnancy-Related Glycodelin-A
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db10-1186
UR  - http://diabetes.diabetesjournals.org/content/60/3/909.abstract
VL  - 60
ER  -
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