Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach
Joint Authors
Asif, Abdul R.
Misdaq, Misbah
Ziegler, Sonia
von Ahsen, Nicolas
Oellerich, Michael
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-22
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Thiopurines are extensively used immunosuppressants for the treatment of inflammatory bowel disease (IBD).
The polymorphism of thiopurine S-methyltransferase (TPMT) influences thiopurine metabolism and therapy outcome.
We used a TPMT knockdown (kd) model of human Jurkat T-lymphocytes cells to study the effects of treatment with 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) on proteome and phosphoproteome.
We identified thirteen proteins with altered expression and nine proteins with altered phosphorylation signals.
Three proteins (THIO, TXD17, and GSTM3) with putative functions in cellular oxidative stress responses were altered by 6-TG treatment and another protein PRDX3 was differentially phosphorylated in TPMT kd cells.
Furthermore, reactive oxygen species (ROS) assay results were consistent with a significant induction of oxidative stress by both TPMT knockdown and thiopurine treatments.
Immunoblot analyses showed treatment altered expression of key antioxidant enzymes (i.e., SOD2 and catalase) in both wt and kd groups, while SOD1 was downregulated by 6-TG treatment and TPMT knockdown.
Collectively, increased oxidative stress might be a mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e., hepatotoxicity) and an antioxidant cotherapy might help to combat this.
Results highlight the significance of oxidative stress in thiopurines’ actions and could have important implications for the treatment of IBD patients.
American Psychological Association (APA)
Misdaq, Misbah& Ziegler, Sonia& von Ahsen, Nicolas& Oellerich, Michael& Asif, Abdul R.. 2015. Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1072329
Modern Language Association (MLA)
Misdaq, Misbah…[et al.]. Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach. Mediators of Inflammation No. 2015 (2015), pp.1-14.
https://search.emarefa.net/detail/BIM-1072329
American Medical Association (AMA)
Misdaq, Misbah& Ziegler, Sonia& von Ahsen, Nicolas& Oellerich, Michael& Asif, Abdul R.. Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-14.
https://search.emarefa.net/detail/BIM-1072329
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072329