Publication details

The role of ABC transporters associated with multidrug resistance in stem cells

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Authors

LÁNOVÁ Martina VEČEŘA Josef KUČERA Jan MEDALOVÁ Jiřina PACHERNÍK Jiří

Year of publication 2013
Type Appeared in Conference without Proceedings
MU Faculty or unit

Faculty of Science

Citation
Description ATP-binding transporters (ABC-t) play various roles in regulation of organism function and homeostasis from prokaryote to mammals. ABC-t mediate transport mainly of lipophilic substances through cellular membranes. These transporters protect stem cells against toxic substances of either endogenous, or importantly, exogenous origin. These transporters are called ABC-t associated with multi-drug resistance (MDR), according to their role in multidrug resistance to pharmacotherapy. High level of ABC-t expression is a typical feature of stem cells and many types of cancer stem cells. Particularly, ABCB1/P-glycoprotein/MDR1, ABCC1/multidrug resistance-associated protein 1 (MRP1), and ABCG2/BCRP (Breast cancer resistance protein);. However, substrates of ABC-t/MDR are not only toxins, but also important signaling molecules as well as leukotrienes and/or glutathione conjugates; and porphyrins, which mediate balance in intracellular oxidation-reduction processing. Thus we hypothesize the role of ABC-t/MDR in regulation of stem cells fate. To test this hypothesis we analyzed effect of modulation of ABC-t/MDR activity in embryonic and neural stem cells. We observed that ABCC1 and ABCG2 are the most expressed ABC-t/MDR in our tested stem cells. Importantly, inhibition of these ABC-t/MDR leads to decreasing of stemness and induction of differentiation in both embryonic and neural stem cells. Analysis of mechanism of observed effect and identification of studying ABC-t/MDR substrates, which may be responsible for this effect, are in progress.
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