Mycotoxin Altertoxin II Induces Lipid Peroxidation Connecting Mitochondrial Stress Response to NF-κB Inhibition in THP-1 Macrophages
Giorgia Del Favero, Julia Hohenbichler, Raphaela Maria Mayer, Michael Rychlik, Doris Marko
Abstract
. Taking this as a starting point, we investigated the effects of one of the most potent genotoxic compounds produced by this fungi type, namely altertoxin II (ATXII) on THP-1 macrophages. In noncytotoxic concentrations (0.1-1 μM), ATXII inhibited the activation of the transcription factor NF-κB, and this event was accompanied by significant mitochondrial superoxide production (1 μM ATXII). Both responses seemed dependent on membrane structure and morphology since they were modulated by the coincubation with the cholesterol complexing agent methyl-β-cyclodextrin (MβCD, 10-50 μM). Moreover, toxicity of ATXII was enhanced by cholesterol load (cholesterol-MβCD). The mycotoxin induced also lipid peroxidation (1-10 μM, ATXII) possibly streaming down at the mitochondrial level and suppressing NF-κB activation in THP-1 macrophages.