Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Poster Abstracts

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.

107