Publications (2)6.36 Total impact
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Article: Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis.
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ABSTRACT: Aflatoxins (AF) are contaminants of improperly stored foods; they are potent genotoxic and carcinogenic compounds, exerting their effects through damage to DNA. They can also induce mutations that increase oxidative damage. The goal of this study was to evaluate the possibility that a third mechanism could be involved in the carcinogenic action of aflatoxins, namely, direct binding to key enzymes involved in the regulatory pathways of the cell cycle, thereby modulating enzyme functionality. The 20S constitutive and immunoproteasome peptidase and proteolytic activities were assayed in the presence of aflatoxins B1, G1 and M1. All three toxins activated multiple peptidase activities of the proteasome. Aflatoxin (AF) M1 was the most potent activator of proteasome activity, while the constitutive 20S proteasome was specifically stimulated by AFG1. Furthermore, the effects of AFB1 on cultured hepatoma cells were investigated and the various proteasomal activities determined with cell lysates were differently affected. Taking into account the key role of the proteasome in cellular defense against oxidative stress, the carbonyl group content and the activities of antioxidant enzymes in cell lysates were analyzed. The proapoptotic effect of AFB1 was also investigated by measuring caspase-3 activity and cellular levels of p27 and IkappaBalpha.Biological Chemistry 02/2007; 388(1):107-17. · 2.96 Impact Factor -
Article: Binding of recombinant PrPc to human plasminogen: kinetic and thermodynamic study using a resonant mirror biosensor.
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ABSTRACT: Transmissible spongiform encephalopathies are a class of sporadic, genetic and transmissible neurodegenerative diseases that affect both humans and animals. Propagation of these diseases is thought to be due to the misfolding of a neuronal glyco-protein, PrP(c), into a pathological insoluble conformer, PrP(Sc). In earlier works, some serum components were identified as exclusive PrP(Sc)-interacting proteins (Fisher et al., Nature 2000;408:479), and thus those macromolecules were thought to represent a potential diagnostic endogenous factor discriminating between normal and pathological prion proteins. In contrast, in agreement with a recent work (Kornblatt et al., Biochem Biophys Res Commun 2003;305:518), in this paper we present a detailed thermodynamic and kinetic characterization of the interaction between recombinant bovine PrP(c 25-242) and the human serum component plasminogen, measured using a resonant mirror technique: our results reveal a high-affinity interaction between the two binding partners. For comparison, the complex obtained from the purified full-length PrP(c) and human plasminogen was also studied: both prion proteins (the recombinant bovine PrP(c 25-242) and the purified full-length PrP(c)) are able to bind human plasminogen. Both kinetic and thermodynamic parameters are affected by the modulation exerted by the H(+) ions in solution. Moreover, the analysis of binding, according to canonical linkage relationships, suggests the involvement of a His residue, consistent with the interaction between other serine (pro)enzymes and their ligands.Proteins Structure Function and Bioinformatics 03/2005; 58(3):728-34. · 3.39 Impact Factor
