Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine.,Journal of Proteomics

当前位置： X-MOL 学术 › J. Proteomics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine.
Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.jprot.2020.103842
Laura Soler ₁ , Alexandre Stella ₂ , Juan Seva ₃ , Francisco Jose Pallarés ₃ , Tarek Lahjouji ₁ , Odile Burlet-Schiltz ₂ , Isabelle P Oswald ₁

Affiliation

Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is estrogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling and metabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. The exposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possibly implicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objective was to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pig jejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related with an induction of ERα signaling and a consequent disruption of highly interrelated signaling cascades, such as NF-κB, ERK1/2, CDX2 and HIF1α. The toxicity of ZEN leads also to an altered immune status characterized by the activation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect the estrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronic inflammatory disorders.

Significance

The proteomics results presented in our study indicate that the endocrine disruptor activity of ZEN is able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress of intestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in intestinal pathogenesis.

中文翻译：

短暂，无细胞毒性暴露于猪肠道中的霉菌雌激素玉米赤霉烯酮引起的蛋白质组变化。

肠上皮稳态由信号通路的复杂网络调节。其中有雌激素信号传导，对上皮细胞的增殖和分化，免疫信号传导和代谢很重要。霉菌毒素玉米赤霉烯酮（ZEN）是天然存在于食物和饲料中的雌激素破坏剂。肠暴露于ZEN具有毒性作用，包括免疫状态改变，可能与致癌作用有关，但尚不清楚与这些作用有关的分子机制。我们的目标是探索使用猪空肠外植体在肠道中短暂，无细胞毒性地接触ZEN诱导的蛋白质组变化。我们的结果表明ZEN几乎不会促进蛋白质组变化，但与ERα信号的诱导和随后高度相关的信号级联信号（如NF-κB，ERK1 / 2，CDX2和HIF1α）的破坏显着相关。ZEN的毒性还导致免疫状态改变，其特征在于趋化因子CXCR4 / SDF-1轴的激活和MHC-1蛋白的积累。我们的结果将ZEN的雌激素破坏活性与其肠道毒性作用联系在一起，使ZEN的暴露与细胞信号异常相似，而这些信号异常与癌症和慢性炎性疾病等疾病的发作和发展相似。