Responses to oxidative stresses induced by gliadin intake have not been characterized in C. elegans model system. Gliadin is a major protein component of gluten, which causes gluten toxicity in human through intestinal stress. In a previous study, we showed that gliadin intake induces oxidative stress in intestine and reduces fertility in C. elegans. To elucidate the molecular mechanism how intestinal stress affects fertility, we examined intestine and germ line of C. elegans after gliadin treatment. Treatment with gliadin or its synthetic peptides, peptide I (from aa 111-130) and peptide II (from aa 151-170) increased ROS (reactive oxygen species) production, decreased intestinal F-actin intensity, and increased level of germ cell apoptosis observed by H2DCFDA, phalloidin staining, and Acridine Orange staining, respectively. These results suggest that high level of ROS production in the intestine after gliadin intake causes disruption of intestinal epithelium and induces germ cell apoptosis. Gliadin-induced germ cell apoptosis (GIGA) was suppressed by depletion of either
cep-1,
ced-13, or
egl-1 in the germ line. However, HUS-1 was not activated in this process, suggesting that GIGA is CEP-1-dependent but is different from DNA damage response. Furthermore, GIGA was also suppressed by depletion of
let-60 (RAS ortholog) or
mpk-1 (ERK ortholog) in either germ line or soma, indicating that GIGA is activated through the RAS/MAPK pathway in both germ line and somatic tissues. To examine the relationship between intestinal stress and germ cell apoptosis, we treated antioxidant after gliadin intake and we found that both GIGA and F-actin intensity were recovered. Furthermore, we examined GIGA and F-actin intensity in
mev-1 (oxidative stress-sensitive) mutants with or without gliadin treatment.
mev-1 mutants showed additive effects with gliadin treatment and its effects were also recovered with antioxidant treatment. These results suggest that GIGA was induced by ROS production in the intestine and the RAS/MAPK pathway and CEP-1 activity are involved in this process. This study was supported by the National Research Foundation of Korea grant funded by the Korean Ministry of Science and ICT (NRF-2018R1A2B6007915).