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Identification of [CuCl(acac)(tmed)], a copper(II) complex with mixed ligands, as a modulator of Cu,Zn superoxide dismutase (Sod1p) activity in yeast

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Abstract

Superoxide dismutases (SODs) stand in the prime line of enzymatic antioxidant defense in nearly all eukaryotic cells exposed to oxygen, catalyzing the breakdown of the superoxide anionic radical to O2 and H2O2. Overproduction of superoxide correlates with numerous pathophysiological conditions, and although the native enzyme can be used as a therapeutic agent in superoxide-associated conditions, synthetic low molecular weight mimetics are preferred in terms of cost, administration mode, and bioavailability. In this study we make use of the model eukaryote Saccharomyces cerevisiae to investigate the SOD-mimetic action of a mononuclear mixed-ligand copper(II) complex, [CuCl(acac)(tmed)] (where acac is acetylacetonate anion and tmed is N,N,N′,N′-tetramethylethylenediamine). Taking advantage of an easily reproducible phenotype of yeast cells which lack Cu–Zn SOD (Sod1p), we found that the compound could act either as a superoxide scavenger in the absence of native Sod1p or as a Sod1p modulator which behaved differently under various genetic backgrounds.

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Abbreviations

acac:

Acetylacetonate anion

Cu,Zn-SOD:

Copper- and zinc-containing superoxide dismutase

MES:

2-(N-Morpholino)ethanesulfonic acid

Mn-SOD:

Manganese-containing superoxide dismutase

MOPS:

3-(N-Morpholino)propanesulfonic acid

NBT:

Nitro blue tetrazolium

OD600 :

Optical density of the cellular suspension at 600 nm

PQ:

Paraquat

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

SD:

Synthetic complete medium containing 2 % dextrose

SD-K:

Synthetic complete medium containing 2 % dextrose lacking lysine

tmed:

N,N,N′,N′-Tetramethylethylenediamine

Tris:

Tris(hydroxymethyl)methylamine

YPD:

Yeast extract–peptone–dextrose

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Acknowledgments

The authors are grateful to Iuliana Gruia for helpful discussion and technical assistance. This work was supported by the Ministry of Education and Research of Romania through the Grant-in-Aid PNII Idei_965, 176/2007, and by the postdoctoral program POSDRU/89/1.5/S/60746 of the European Social Fund.

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Authors and Affiliations

  1. Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Sos. Panduri 90-92, 050663, Bucharest, Romania

    Ioana Dumitru, Cristian D. Ene, Augustin M. Ofiteru, Codruta Paraschivescu, Ion Baciu & Ileana C. Farcasanu

  2. Department of Inorganic Chemistry, University of Bucharest, Dumbrava Rosie 23, 020464, Bucharest, Romania

    Augustin M. Madalan

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  1. Ioana Dumitru
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  2. Cristian D. Ene
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Correspondence to Ileana C. Farcasanu.

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I. Dumitru and C.D. Ene contributed equally to this work.

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Dumitru, I., Ene, C.D., Ofiteru, A.M. et al. Identification of [CuCl(acac)(tmed)], a copper(II) complex with mixed ligands, as a modulator of Cu,Zn superoxide dismutase (Sod1p) activity in yeast. J Biol Inorg Chem 17, 961–974 (2012). https://doi.org/10.1007/s00775-012-0912-1

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