Thiopurine S-methyltransferase is involved in oxidoreductive processes and influences cell redox capacity [Elektronski vir]
Šmid, Alenka, farmacevtka ...
Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in deactivation of thiopurines which are used in the treatment of acute lymphoblastic leukemia, inflammatory bowel disease and ...autoimmune disorders. TPMT represents a major determinant of thiopurine-related toxicities and 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 matrix factorization-based data fusion approach to analyse wholegenome expression data from 1024 healthy individuals combined with gene ontologies and proteinprotein interactions databases. The results suggest that TPMT is closely related to genes involved in oxidoreductive processes. The in vitro experiments on different cell models confirmed that TPMT status influences cell redox capacity by altering SAM consumption and consequently GSH synthesis. Understanding of TPMT's endogenous role will allow for further improvement of individualized therapy with thiopurines.
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