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Article: Glycosylation failure extends to glycoproteins in gestational diabetes mellitus: Evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-A

TitleGlycosylation failure extends to glycoproteins in gestational diabetes mellitus: Evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-A
Authors
Issue Date2011
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2011, v. 60 n. 3, p. 909-917 How to Cite?
AbstractOBJECTIVE - 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. © 2011 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/135677
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Biotechnology and Biological Sciences Research CouncilBBF0083091
Helsinki University Central Hospital
Academy of Finland
Funding Information:

P.-C.P., H.R.M., B.T., M.P., and A.D. were supported by the Biotechnology and Biological Sciences Research Council (BBF0083091), and R.K., H.K., and M.S. were supported by grants from the Helsinki University Central Hospital Research Fund and the Academy of Finland.

References

 

DC FieldValueLanguage
dc.contributor.authorLee, CLen_HK
dc.contributor.authorChiu, PCNen_HK
dc.contributor.authorPang, PCen_HK
dc.contributor.authorChu, IKen_HK
dc.contributor.authorLee, KFen_HK
dc.contributor.authorKoistinen, Ren_HK
dc.contributor.authorKoistinen, Hen_HK
dc.contributor.authorSeppälä, Men_HK
dc.contributor.authorMorris, HRen_HK
dc.contributor.authorTissot, Ben_HK
dc.contributor.authorPanico, Men_HK
dc.contributor.authorDell, Aen_HK
dc.contributor.authorYeung, WSBen_HK
dc.date.accessioned2011-07-27T01:39:13Z-
dc.date.available2011-07-27T01:39:13Z-
dc.date.issued2011en_HK
dc.identifier.citationDiabetes, 2011, v. 60 n. 3, p. 909-917en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135677-
dc.description.abstractOBJECTIVE - 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. © 2011 by the American Diabetes Association.en_HK
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subject.meshAmniotic Fluid - metabolism-
dc.subject.meshDiabetes, Gestational - metabolism-
dc.subject.meshGlycoproteins - metabolism-
dc.subject.meshN-Acetylneuraminic Acid - metabolism-
dc.subject.meshPregnancy Proteins - metabolism-
dc.titleGlycosylation failure extends to glycoproteins in gestational diabetes mellitus: Evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-Aen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=60&issue=3&spage=909&epage=917&date=2011&atitle=Glycosylation+failure+extends+to+glycoproteins+in+gestational+diabetes+mellitus:+evidence+from+reduced+α2-6+sialylation+and+impaired+immunomodulatory+activities+of+pregnancy-related+glycodelin-Aen_US
dc.identifier.emailChiu, PCN:pchiucn@hku.hken_HK
dc.identifier.emailChu, IK:ivankchu@hku.hken_HK
dc.identifier.emailLee, KF:ckflee@hku.hken_HK
dc.identifier.emailYeung, WSB:wsbyeung@hkucc.hku.hken_HK
dc.identifier.authorityChiu, PCN=rp00424en_HK
dc.identifier.authorityChu, IK=rp00683en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.identifier.authorityYeung, WSB=rp00331en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.2337/db10-1186en_HK
dc.identifier.pmid21300843-
dc.identifier.pmcidPMC3046852-
dc.identifier.scopuseid_2-s2.0-79952374032en_HK
dc.identifier.hkuros188136en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79952374032&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue3en_HK
dc.identifier.spage909en_HK
dc.identifier.epage917en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000288060300026-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, CL=9277221100en_HK
dc.identifier.scopusauthoridChiu, PCN=25959969200en_HK
dc.identifier.scopusauthoridPang, PC=23028555800en_HK
dc.identifier.scopusauthoridChu, IK=7103327484en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK
dc.identifier.scopusauthoridKoistinen, R=7006574669en_HK
dc.identifier.scopusauthoridKoistinen, H=7003612125en_HK
dc.identifier.scopusauthoridSeppälä, M=35475165300en_HK
dc.identifier.scopusauthoridMorris, HR=7401534652en_HK
dc.identifier.scopusauthoridTissot, B=14621721100en_HK
dc.identifier.scopusauthoridPanico, M=7005321077en_HK
dc.identifier.scopusauthoridDell, A=7103412653en_HK
dc.identifier.scopusauthoridYeung, WSB=7102370745en_HK
dc.identifier.citeulike8835603-

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