The role of ATP-binding transporters associated with multi-drug 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 organism function and homeostasis from prokaryota to mammals. ABC-t mediate transport of mainly lipophilic substances through cellular membranes. Some ABC-t are important in cell protection against endogenous and importantly also exogenous toxins. These transporters are called ABC-t associated with multi-drug resistance (ABC-t/MDR), according to their role in resistance of tumor cells to pharmacotherapy. ABC-t/MDR are also over-expressed in stem cells, where their protective role is expected, too. Particularly, ABCB1, ABCC1, and ABCG2 are common ABC-t/MDR expressed in stem cells. However, substrates of ABC-t/MDR are not only toxins, but also important signaling molecules as well leukotrienes and/or glutathione conjugates and porphyrins, which mediated balance in intracellular oxidation-reduction processing. Thus we hypothesize the role of ABC-t/MDR also 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 progression.
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