ERK1/2-mediated autophagy is essential for cell survival under Ochratoxin A exposure in IPEC-J2 cells

The intestinal epithelium represents the first physical barrier against food contaminations. Ochratoxin A (OTA), one of the most deleterious mycotoxins, is commonly detected in food and feed stuff. The purpose of this study is to explore the adaptive cyto-protection of intestinal epithelium against OTA exposure and relevant regulation mechanisms. The intestinal porcine epithelial cell line (IPEC-J2) was applied as in vitro models for intestinal epithelium. Western blot and immunofluorescence analysis confirmed that OTA induced extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) activation in IPEC-J2 cells. Hoechst 33258 staining and Annexin V/PI analysis exhibited that U0126, the ERK1/2 inhibitor, aggravated OTA-induced apoptosis. Then, we observed that OTA could induce autophagy by western blot. Furthermore, OTA-induced autophagy could be inhibited by U0126. Chloroquine (CQ), the autophagy inhibitor, enhanced OTA-induced apoptosis in IPEC-J2 cells. In addition, CQ aggravated the production of mitochondrial reactive oxygen species, the release of cytochrome c release, and the activation of caspase-3. Taken together, these results suggest that ERK1/2-mediated autophagy is required for porcine intestinal epithelial cell survival against OTA toxicity.