Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.
Division of Nutrition and Metabolism Research, Korea Food Research Institute, Jeollabuk-do 55365, Korea.
Nutrients. 2019 Oct 27;11(11):2587. doi: 10.3390/nu11112587.
Gliadin is a major protein component of gluten and causes gluten toxicity through intestinal stress. We previously showed that gliadin intake induces oxidative stress in the intestine and reduces fertility in a model. To elucidate the possible link between intestinal stress and reproduction, changes in the intestine and germ cells of after gliadin intake were examined at the molecular level. Gliadin intake increased reactive oxygen species (ROS) production in the intestine, decreased intestinal F-actin levels, and increased germ cell apoptosis. These gliadin-triggered effects were suppressed by antioxidant treatment. These results suggest that ROS production in the intestine induced by gliadin intake causes disruption of intestinal integrity and increases germ cell apoptosis. Gliadin-induced germ cell apoptosis (GIGA) was suppressed by depletion of , , , or . However, HUS-1 was not activated, suggesting that GIGA is activated through the mitogen-activated protein kinase (MAPK) pathway and is CEP-1-dependent but is a separate pathway from that controlling the DNA damage response. Taken together, our results suggest that gliadin causes intestinal barrier disruption through ROS production and interacts with the germ cells to reduce fertility through GIGA.
麦醇溶蛋白是谷蛋白的主要蛋白质成分,通过肠道应激引起谷蛋白毒性。我们之前的研究表明,麦醇溶蛋白摄入会在肠道中诱导氧化应激,并降低模型中的生育能力。为了阐明肠道应激与生殖之间的可能联系,在分子水平上检查了麦醇溶蛋白摄入后 肠道和生殖细胞的变化。麦醇溶蛋白摄入增加了肠道中活性氧(ROS)的产生,降低了肠道 F-肌动蛋白水平,并增加了生殖细胞凋亡。抗氧化剂处理抑制了这些由麦醇溶蛋白引发的作用。这些结果表明,麦醇溶蛋白摄入诱导的肠道中 ROS 的产生导致肠道完整性的破坏,并增加生殖细胞凋亡。通过耗尽 、 、 或 可以抑制麦醇溶蛋白诱导的生殖细胞凋亡(GIGA)。然而,HUS-1 未被激活,表明 GIGA 通过丝裂原活化蛋白激酶(MAPK)途径激活,并且依赖于 CEP-1,但与控制 DNA 损伤反应的途径不同。总之,我们的结果表明,麦醇溶蛋白通过 ROS 产生引起肠道屏障破坏,并通过 GIGA 与生殖细胞相互作用降低生育能力。