Identification of [CuCl(acac)(tmed)], a copper(II) complex with mixed ligands, as a modulator of Cu,Zn superoxide dismutase (Sod1p) activity in yeast.
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 O(2) and H(2)O(2). 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.
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, Bucharest, Romania.
Ioana
I
Dumitru
Cristian D
CD
Ene
Augustin M
AM
Ofiteru
Codruta
C
Paraschivescu
Augustin M
AM
Madalan
Ion
I
Baciu
Ileana C
IC
Farcasanu
D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008024:Ligands; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C491960:CCS1 protein, S cerevisiae; D056831:Coordination Complexes; D008024:Ligands; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins