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Licensed Unlicensed Requires Authentication Published by De Gruyter February 5, 2014

Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B

  • Paraskevi Moutsatsou , James N. Tsoporis EMAIL logo , Vasileios Salpeas , Ekaterini Bei , Basel Alevizos , Chrysoula Anagnostara , Shehla Izhar , Gerald Proteau , Emmanouil Rizos , Erifili Hatziagelaki , Ioannis K. Toumpoulis , Ioannis K. Rizos and Thomas G. Parker


Background: This study addresses the expression of the glycosylated proteins known as advanced glycation end products (AGEs), the calcium binding protein S100B and the apoptotic parameters cytochome c and caspase-3 activity in peripheral lymphocyte cytosolic extracts from a sample of bipolar disorder (BD) patients and healthy (control) subjects.

Methods: Cross-sectional study of 35 patients with a clinical diagnosis of bipolar disease (10 euthymic, 12 depressed, 13 manic) and 10 healthy control subjects. Lymphocytes were used as a surrogate model in BD diagnosis and treatment. AGEs and S100B in lymphocyte cell extracts were measured by commercially available enzyme-linked immunosorbent assay.

Results: AGEs were lower in all BD patients compared to healthy subjects. Depressed patients had approximately two-fold higher S100B levels compared to healthy subjects. Manic and depressed BD patients had increased superoxide dismutase mRNA levels. Apoptosis as measured by BAX/Bcl2 ratio, cytochrome c release, caspase-3 activity was increased in manic and depressed patients compared to healthy subjects. In the depressed patients, S100B levels correlated with cytochrome c release.

Conclusions: In conclusion, our study shows decreased AGEs and increased S100B levels and caspase down-stream apoptosis in peripheral lymphocytes of BD patients that may underlie disease etiopathogenesis.

Corresponding author: James N. Tsoporis, Division of Cardiology, Department of Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada, Phone: +1 416-864-6060X77625, Fax: +1 416-864-6034, E-mail:
aParaskevi Moutsatsou and James N. Tsoporis contributed equally to this work.


This project is financed from an operating grant to TGP from the Canadian Institutes of Health Research.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


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Received: 2013-11-12
Accepted: 2014-1-10
Published Online: 2014-2-5
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

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