title: Antipsychotic treatment of acute paranoid schizophrenia patients with olanzapine results in altered glycosylation of serum glycoproteins.
abstract: Atypical antipsychotic drugs, such as olanzapine, have been shown to alleviate the positive, negative and, to a lesser degree, the cognitive symptoms of schizophrenia in many patients. However, the detailed mechanisms of action of these drugs have yet to be elucidated. We have carried out the first investigation aimed at evaluating the effects of olanzapine treatment on the glycosylation of serum proteins in schizophrenia patients. Olanzapine treatment resulted in increased levels of a disialylated biantennary glycan and reduced levels of a number of disialylated bi- and triantennary glycans on whole serum glycoproteins. These changes were not observed on a low-abundance serum protein fraction. α1 acid glycoprotein was identified as a carrier of some of the detected altered oligosaccharides. In addition, glycan analysis of haptoglobin, transferrin, and α1 antitrypsin reported similar findings, although these changes did not reach significance. Exoglycosidase digestion analysis showed that olanzapine treatment increased galactosylation and sialylation of whole serum proteins, suggesting increased activity of specific galactosyltransferases and increased availability of galactose residues for sialylation. Taken together, these findings indicate that olanzapine treatment results in altered glycosylation of serum proteins.
authors.affiliation: NIBRT Dublin-Oxford Glycobiology Laboratory, National Institute for Bioprocessing Research and Training, Foster Avenue, Mount Merrion, Co., Dublin, Ireland.
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Telford
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bones
authors.forename: Ciara
authors.initials: C
authors.lastname: McManus
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.forename: Gwen
authors.initials: G
authors.lastname: Manning
authors.forename: Margaret
authors.initials: M
authors.lastname: Doherty
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.forename: Matthias
authors.initials: M
authors.lastname: Rothermundt
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D000208:Acute Disease; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D005260:Female; D054794:Glycomics; D006023:Glycoproteins / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D009961:Orosomucoid / Q000378:metabolism; D011134:Polysaccharides / Q000097:blood; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012563:Schizophrenia, Paranoid / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; D006023:Glycoproteins; D009961:Orosomucoid; D011134:Polysaccharides; D000515:alpha 1-Antitrypsin; D001569:Benzodiazepines; D000077152:Olanzapine