Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis

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.

Toxic effect of aflatoxin B1 and the role of recovery on the rat cerebral cortex and hippocampus

“…The aflatoxin-mediated neuronal and cellular loss could potentially be explained by several mechanisms; first, aflatoxin or its metabolites might interact with some components of the cells such as nucleic acid, protein and key enzymes involved in regulatory pathways of cell cycle and triggers the process of apoptosis (Amici et al, 2007;Martins et al, 2007). Second, aflatoxins significantly inhibit acetylcholinesterase activity in the brain and spinal cord which may result in nerve cell degeneration (Cometa et al, 2005).…”

In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes

“…AFB1 toxicity is also related to LPO and oxidation of DNA in vivo and in vitro (Shen et al 1996). So this xenobiotic could contribute to the modification of the genome leading to carcinogenesis (Amici et al 2007). Lipid peroxides enter the nucleus where they react with Fe ?2 to generate the alkoxyl radical which attacks DNA (Fraga and Tappel 1988).…”

Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

“…AFB 1 toxicity is also related to LPO and oxidation of DNA in vivo and in vitro (Shen et al 1996). Thus, the genome formation leading to carcinogenesis could be occured by this xenobiotic (Amici et al 2007). Lipid peroxides enter the nucleus where they react with Fe ?2 to generate the alkoxyl radical which attacks DNA (Fraga and Tappel 1988).…”