Titel
Mycotoxin Altertoxin II Induces Lipid Peroxidation Connecting Mitochondrial Stress Response to NF-κB Inhibition in THP-1 Macrophages
Autor*in
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Abstract
Prolonged exposure to mycotoxins, even in subtoxic concentrations, might contribute to modulate pro- or anti-inflammatory cascades and ultimately have long-term consequences on our health. In line, there is an increasing need to describe and comprehend the potential immunomodulatory effects of toxins that can be produced from fungi proliferating even in a domestic environment like, for instance, Alternaria alternata. 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.
Stichwort
ImmunologyMembranesOxidesPeptides and proteinsToxins
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Chemical Research in Toxicology
Band
33
Ausgabe
2
ISSN
0893-228X
Erscheinungsdatum
2020
Seitenanfang
492
Seitenende
504
Publication
American Chemical Society (ACS)
Erscheinungsdatum
2020
Zugänglichkeit
Rechte
Rechteangabe
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