NDLI: Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins altertoxin I and II

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Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins altertoxin I and II

Content Provider	Springer Nature Link
Author	Jarolim, Katharina Del Favero, Giorgia Pahlke, Gudrun Dostal, Victoria Zimmermann, Kristin Heiss, Elke Ellmer, Doris Stark, Timo D. Hofmann, Thomas Marko, Doris
Copyright Year	2016
Abstract	The mycotoxins altertoxin I and II (ATX I and II) are secondary metabolites produced by Alternaria alternata fungi and may occur as food and feed contaminants, especially after long storage periods. Although the toxic potential of altertoxins has been previously investigated, little is known about the pathways that play a role in their intracellular metabolism. In order to identify potential targets of ATX I and ATX II, the two toxins were tested for interaction with the nuclear factor erythroid-derived 2-like 2/antioxidant response element (Nrf2/ARE) pathway in mammalian cells. This pathway can be activated by various stressors resulting in the expression of enzymes important for metabolism and detoxification. In the present study, only ATX II triggered a concentration-dependent increase in Nrf2-ARE-dependent luciferase expression. Consistently, confocal microscopy revealed an ATX II-induced increase in Nrf2 signal in HT29 intestinal cells. In agreement with these data, ATX II induced the transcription of γ-glutamate cysteine ligase, the key enzyme in catalyzing GSH synthesis of the cells and which is regulated by Nrf2. Further investigations demonstrated that ATX II induced a concentration-dependent depletion of the cellular GSH levels after short incubation time (3 h) and an increase after longer incubation time (24 h). In conclusion, it was demonstrated that ATX II can interact at several levels of the Nrf2-ARE pathway in mammalian cells and that ATX I does not share the same mechanism of action.
Starting Page	203
Ending Page	216
Page Count	14
File Format	PDF
ISSN	03405761
Journal	Archives of Toxicology
Volume Number	91
Issue Number	1
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-05-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alternaria alternata Altertoxin I (ATX I) Altertoxin II (ATX II) Nrf2 Glutathione Confocal/SIM microscopy Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

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