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Interaction between lanthanide ions and Saccharomyces cerevisiae cells

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Abstract

Lanthanides are a group of non-essential elements with important imaging and therapeutic applications. Although trivalent lanthanide ions (Ln3+) are used as potent blockers of Ca2+ channels, the systematic studies correlating Ln3+ accumulation and toxicity to Ca2+ channel blocking activity are scarce. In this study, we made use of the eukaryotic model Saccharomyces cerevisiae to investigate the correlation between Ln3+ accumulation, their toxicity and their capacity to block the exogenous stress-induced Ca2+ influx into the cytosol. It was found that the Ln3+ blocked the Ca2+ entry into the yeast cells only when present at concentration high enough to allow rapid binding to cell surface. At lower concentrations, Ln3+ were taken up by the cell, but Ca2+ blockage was no longer achieved. At 1 mM concentration, all ions from the Ln3+ series could block Ca2+ entry into cytosol with the exception of La3+, and to a lesser extent, Pr3+ and Nd3+. The plasma membrane Ca2+-channel Cch1/Mid1 contributed to La3+ and Gd3+ entry into the cells, with a significant preference for La3+. The results open the possibility to obtain cells loaded with controlled amounts and ratios of Ln3+.

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Abbreviations

[Ca2+]cyt :

Cytosolic Ca2+

CFU:

Colony forming units

EDTA:

Ethylenediaminetetraacetic acid

ICP-MS:

Inductively coupled plasma-mass spectrometry

Ln3+ :

Trivalent lanthanide ions

MES:

2-(N-morpholino)ethanesulfonic acid

MM:

Minimal defined medium

RLU:

Relative luminescence units

SD-Ura:

SD lacking uracil

SE:

Standard deviation

WT:

Parental “wild-type” strain

YPD:

Yeast extract-peptone-dextrose

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Acknowledgments

The authors acknowledge the contribution of Prof. Enzo Martegani and Dr. Renata Tisi (from University of Milano-Bicocca, Milan, Italy) to the manuscript by generously providing the plasmid pYX212-cytAEQ and thank Dr. Andrei F. Danet for technical support. The research leading to these results has received funding from the Romania-EEA Research Programme operated by the Ministry of National Education under the EEA Financial Mechanism 2009–2014 and Project Contract No 21 SEE/30.06.2014, and by the Executive Unit for Higher Education, Development, Research and Innovation Funding—UEFISCDI, Romania, under Grant PN-II-PT-PCCA-2013-4-0291 (contract no. 203/2014). C. D. E. was a recipient of a postdoctoral fellowship POSDRU/89/1.5/S/60746 when the study was initiated.

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Correspondence to Ileana C. Farcasanu.

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Ene, C.D., Ruta, L.L., Nicolau, I. et al. Interaction between lanthanide ions and Saccharomyces cerevisiae cells. J Biol Inorg Chem 20, 1097–1107 (2015). https://doi.org/10.1007/s00775-015-1291-1

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  • DOI: https://doi.org/10.1007/s00775-015-1291-1

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