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      Cytotoxicity of Oleandrin Is Mediated by Calcium Influx and by Increased Manganese Uptake in Saccharomyces cerevisiae Cells

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          Abstract

          Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na +/K +-ATPases and subsequent increase in cell calcium, many aspects which determine oleandrin cytotoxicity remain elusive. In this study, we used the model Saccharomyces cerevisiae to unravel new elements accounting for oleandrin toxicity. Using cells expressing the Ca 2+-sensitive photoprotein aequorin, we found that oleandrin exposure resulted in Ca 2+ influx into the cytosol and that failing to pump Ca 2+ from the cytosol to the vacuole increased oleandrin toxicity. We also found that oleandrin exposure induced Mn 2+ accumulation by yeast cells via the plasma membrane Smf1 and that mutants with defects in Mn 2+ homeostasis are oleandrin-hypersensitive. Our data suggest that combining oleandrin with agents which alter Ca 2+ or Mn 2+ uptake may be a way of controlling oleandrin toxicity.

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          A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding

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            Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.

            A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed. These strains minimize or eliminate the homology to the corresponding marker genes in commonly used vectors without significantly affecting adjacent gene expression. Because the homology between commonly used auxotrophic marker gene segments and genomic sequences has been largely or completely abolished, these strains will also reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications. We also report the construction of new members of the pRS400 series of vectors, containing the kanMX, ADE2 and MET15 genes.
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              Getting started with yeast.

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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                17 September 2020
                September 2020
                : 25
                : 18
                : 4259
                Affiliations
                Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Sos. Panduri 90-92, 050663 Bucharest, Romania; lavinia.ruta@ 123456chimie.unibuc.ro (L.L.R.); valentina.popa@ 123456chimie.unibuc.ro (C.V.P.)
                Author notes
                [* ]Correspondence: ileana.farcasanu@ 123456chimie.unibuc.ro ; Tel.: +40-721-067-169
                Author information
                https://orcid.org/0000-0001-9287-5485
                https://orcid.org/0000-0002-4901-7896
                Article
                molecules-25-04259
                10.3390/molecules25184259
                7570853
                32957533
                db926d00-8940-44c9-bf1c-947574138589
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 August 2020
                : 15 September 2020
                Categories
                Article

                oleandrin,saccharomyces cerevisiae,calcium,manganese
                oleandrin, saccharomyces cerevisiae, calcium, manganese

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