Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis
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Manila Amici
, Valentina Cecarini , Assuntina Pettinari , Laura Bonfili , Mauro Angeletti , Simone Barocci , Massimo Biagetti , Evandro Fioretti and Anna Maria Eleuteri
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 IκBα.
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Articles in the same Issue
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Articles in the same Issue
- Accumulation of viroid-specific small RNAs and increase in nucleolytic activities linked to viroid-caused pathogenesis
- Characterisation of Plasmodium falciparum RESA-like protein peptides that bind specifically to erythrocytes and inhibit invasion
- Structural modifications to a high-activity binding peptide located within the PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus monkeys
- Characterisation of YtfM, a second member of the Omp85 family in Escherichia coli
- Presence of the propeptide on recombinant lysosomal dipeptidase controls both activation and dimerization
- Conformational studies on Arabidopsis sulfurtransferase AtStr1 with spectroscopic methods
- Glycine-assisted enhancement of 1,4-β-d-xylan xylanohydrolase activity at alkaline pH with a pH optimum shift
- Asef is a Cdc42-specific guanine nucleotide exchange factor
- Metal-binding sites at the active site of restriction endonuclease BamHI can conform to a one-ion mechanism
- Interaction of the cellular prion protein with raft-like lipid membranes
- Tissue-specific transcription factor HNF4α inhibits cell proliferation and induces apoptosis in the pancreatic INS-1 β-cell line
- Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis
- The insect metalloproteinase inhibitor gene of the lepidopteran Galleria mellonella encodes two distinct inhibitors
- Activation profiles of the zymogen of aspergilloglutamic peptidase