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Copper-glutathione complexes under physiological conditions: Structures in solution different from the solid state coordination
No full textOxidative stress induced by a di-Schiff base copper complex is both mediated and modulated by glutathione
No full textThe reductive activation of N,N'-bis(2-pyridylmethylene)-1-4-butanediamine (N,N',N",N"')-Cu(II)-diperchlorate (CuPUPY), a di-Schiff base copper complex with antineoplastic properties, was investigated in vitro in the presence of glutathione, ascorbate, NADH or NADPH. Glutathione and ascorbate but not the pyridine dinucleotides were able to reduce the compound. The apparent second order rate constants of the reduction reaction (9.6 +/- 2.0 M-1 sec-1 for ascorbate and 94.7 +/- 1.9 M-1 sec-1 for glutathione) indicate that glutathione is more effective by about one order of magnitude in reducing CuPUPY than ascorbate. Reduction by glutathione triggered a CuPUPY-supported redox-cycle with oxygen yielding H2O2. Whereas reduction by ascorbate was reversible, CuPUPY reduced by glutathione reacted with excess reduced glutathione (GSH) in a ligand exchange reaction yielding a GSH-Cu(I) complex which was reoxidized by O2, forming a complex between copper(II) and oxidized glutathione. These results suggest a dual role for the reduced thiol tripeptide; promoting oxidative stress induced by CuPUPY at low concentrations and inhibiting it at high concentrations. This hypothesis was verified by showing that optimum glutathione/CuPUPY ratios are needed in order to obtain maximum oxidative damage to both DNA and albumin in vitro. Evidence was obtained for the occurrence of the same reaction pathway in human K562 erythroleukemia cells: CuPUPY was more toxic to cells in which glutathione synthesis was inhibited by buthionine sulfoximine. Moreover, ESR spectroscopy revealed alterations in the hyperfine structure of the Cu(II) spectrum, consistent with the occurrence of ligand-exchange reactions in K562 cells
Copper complexes with superoxide dismutase activity enhance oxygen-mediated toxicity in human erythroleukemia cells
No full textCopper-dependent metabolism of Cu,Zn-superoxide dismutase in human K562 cells. Lack of specific transcriptional activation and accumulation of a partially inactivated enzyme
No full textThe regulation of Cu,Zn-superoxide dismutase by copper was investigated in human K562 cells. Copper ions caused a dose- and time-dependent increase, up to 3-fold, of the steady-state level of Cu,Zu-superoxide dismutase mRNA. A comparable increase was also observed for actin and ribosomal protein L32 mRNAs, but not for metallothionein mRNA which was augmented more than 50-fold and showed a different induction pattern. The copper-induced mRNAs were actively translated as judged from their enhanced loading on polysomes, the concomitantly increased cellular protein levels and an augmented incorporation of [3H]lysine into acid-precipitable material. Cu,Zn-superoxide dismutase protein followed this general trend, as demonstrated by dose- and time-dependent increases in immunoreactive and enzymically active protein. However, a specific accumulation of Cu,Zn-superoxide dismutase was noticed in cells grown in the presence of copper, that was not detectable for other proteins. Purification of the enzyme demonstrated that Cu,Zn-superoxide dismutase was present as a reconstitutable, copper-deficient protein with high specific activity (kcat./Cu = 0.89 x 10(9) M-1.s-1) in untreated K562 cells and as a fully metallated protein with low specific activity (kcat./Cu = 0.54 x 10(9) M-1.s-1) in copper-treated cells. Pulse-chase experiments using [3H]lysine indicated that turnover rates of Cu,Zn-superoxide dismutase in K562 cells were not affected by growth in copper-enriched medium, whereas turnover of total protein was significantly enhanced as a function of metal supplementation. From these results we conclude that: (i) unlike in yeast [Carrì, Galiazzo, Ciriolo and Rotilio (1991) FEBS Lett. 278, 263-266] Cu,Zn-superoxide dismutase is not specifically regulated by copper at the transcriptional level in human K562 cells, suggesting that this type of regulation has not been conserved during the evolution of higher eukaryotes; (ii) copper ions cause an inactivation of the enzyme in intact K562 cells; and (iii) the metabolic stability of Cu,Zn-superoxide dismutase results in its relative accumulation under conditions that lead to increased protein turnover
Cytotoxicity of a low molecular weight Cu2Zn2 superoxide dismutase active center analog in human erythroleukemia cells
No full textThe cytotoxicity of SOD-mimics was studied in human K562 erythroleukemia cells. CuPUPY, a low molecular weight copper complex with properties typical of a Cu2Zn2 SOD active center analog was shown to display pronounced toxicity upon incubation with human K562 erythroleukemia cells, while the ligand, CuSO4 or CuEDTA did not affect vitality. Externally added catalase decreased the cytotoxic effects of CuPUPY by 50% indicating an involvement of hydrogen peroxide in toxicity. An increased oxygen uptake and glutathione oxidation by K562 cells in the presence of CuPUPY suggested that toxicity might be due to a copper-mediated redox-cycle. In fact addition of glutathione to a solution of CuPUPY resulted in glutathione oxidation, O2-consumption and H2O2-generation. CuPUPY proved to be less toxic to human lymphocytes than to K562 cells. This selectivity may be related to the low content of antioxidative enzymes in K562 cells
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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