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Single-Cell Biophysics: Measurement, Modulation, and Modeling
Poster Abstracts
107
18-POS
Board 9
The Intestinal Challenge: Combinatory Effect of Shear Stress and Alternaria Alternata
Mycotoxin Altertoxin II (ATXII)
Giorgia Del Favero
, Doris Marko.
University of Vienna, Faculty of Chemistry, Vienna, Austria.
Intestinal cells are continuously subject to biomechanical stimulation, both as a result of the
movement of the fluids into the lumen, and due to the peristaltic contraction of the organ. In this
respect, the performance of cytotoxicity studies in a mechanically stimulated environment is of
crucial importance. Mycotoxins are prevalent food contaminants, in fact, being produced as
secondary metabolites of molds, they can easily contaminate food commodities. Among the
emerging challenges of food toxicology there is ATXII, a genotoxic compound produced by
fungi of Alternaria spp. In human colon carcinoma cells (HT-29), ATXII is severely cytotoxic
and triggers the activation of the Nrf2/ARE pathway [1]. Being Nrf2 translocation particularly
sensitive to shear stress [2-4], the cross-talk between ATXII and the Nrf2 pathway was
investigated in two different models of intestinal cells (HT-29 and HCEC-1CT human colonic
epithelial cells) in static conditions and in presence of shear stress. The effect on cellular
morphology and on Nrf2 localization was monitored by confocal microscopy. ATXII proved to
have a direct effect on Nrf2 translocation, as well as an impact on the actin cytoskeleton, which
appeared to be modulated by shear stress. Moreover, differential response was observed between
tumor and non-transformed cells. Taken together, these findings suggest that the effect of ATXII
can interplay with shear stress and open new perspectives into the understanding of the
mechanisms of action of this emerging mycotoxin.
[1]. Jarolim, K., et al., Arch Toxicol, 2017. 91(1): p. 203-216. [2]. Chen, X.L., et al., J Biol
Chem, 2003. 278(2): p. 703-11.
[3]. Healy, Z.R., et al., Proc Natl Acad Sci U S A, 2005. 102(39): p. 14010-5. [4]. Hosoya, T., et
al., J Biol Chem, 2005. 280(29): p. 27244-50.