Patulin is a
mycotoxin mainly found in apple and apple products. In addition to being toxic for animals, mutagenic, carcinogenic and teratogenic,
patulin induces intestinal
injuries, including epithelial cell degeneration,
inflammation, ulceration, and
hemorrhages. In a study of the cellular mechanisms associated with the intestinal toxicity of
patulin, two human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14) were exposed to the
mycotoxin. Micromolar concentrations of
patulin were found to induce a rapid and dramatic decrease of transepithelial resistance (TER) in both cell lines without major signs of toxicity as assessed by the LDH release assay. Since TER reflects the organization of tight junctions, these data indicate that
patulin affected the barrier function of the intestinal epithelium. The inhibitory effect of
patulin on TER was closely associated with its reactivity for SH groups: (i)
cysteine and
glutathione prevented the cells from
patulin injury; (ii)
patulin toxicity was potentiated by
buthionine sulfoximine, a specific
glutathione-depleting agent; (iii) treatment of the cells with
N-ethylmaleimide, a compound known to react with SH groups, resulted in a marked decrease of TER. Moreover, the inhibitory effect of
patulin on TER was mimicked and potentiated by
phenylarsine oxide, a specific inhibitor of
protein tyrosine phosphatase (PTP). This cellular
enzyme is a key regulator of intestinal epithelial barrier function. The active site of PTP contains a
cysteine residue (Cys215) that is essential for
phosphatase activity. Sulfhydryl-reacting compounds such as
acetaldehyde decrease TER through covalent modification of Cys215 of PTP. We propose that the toxicity of
patulin for intestinal cells involves, among other potential mechanisms, an inactivation of the active site of PTP.