Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Transcriptome analysis reveals involvement of thiopurine S-methyltransferase in oxidation-reduction processes

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB
[thumbnail of Supplementary Material] MS Word (Supplementary Material)
294kB

Item Type:Article
Title:Transcriptome analysis reveals involvement of thiopurine S-methyltransferase in oxidation-reduction processes
Creators Name:Šmid, A., Štajdohar, M., Milek, M., Urbančič, D., Karas Kuželički, N., Tamm, R., Metspalu, A. and Mlinarič-Raščan, I.
Abstract:Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in the deactivation of thiopurines and represents a major determinant of thiopurine-related toxicities. Despite its well-known importance in thiopurine metabolism, the understanding of its endogenous role is lacking. In the present study, we aimed to gain insight into the molecular processes involving TPMT by applying a data fusion approach to analyze whole-genome expression data. The RNA profiling was done on whole blood samples from 1017 adult male and female donors to the Estonian biobank using Illumina HTv3 arrays. Our results suggest that TPMT is closely related to genes involved in oxidoreductive processes. The in vitro experiments on different cell models confirmed that TPMT influences redox capacity of the cell by altering S-adenosylmethionine (SAM) consumption and consequently glutathione (GSH) synthesis. Furthermore, by comparing gene networks of subgroups of individuals, we identified genes, which could have a role in regulating TPMT activity. The biological relevance of identified genes and pathways will have to be further evaluated in molecular studies.
Keywords:Thiopurine S-Methyltransferase, Transcriptome, Data Fusion By Matrix Factorization, Oxidation–Reduction Processes, RNA Microarray Profiling
Source:European Journal of Pharmaceutical Sciences
ISSN:0928-0987
Publisher:Elsevier
Volume:192
Page Range:106616
Number of Pages:1
Date:1 January 2024
Official Publication:https://doi.org/10.1016/j.ejps.2023.106616
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library