Abstract：
Zearalenone (ZEA), a mycotoxin produced by Fusarium, can cause reproductive disorders by targeting ovarian granulosa cells (GCs). We previous showed that scutellarin (Scu) rescues ZEA-induced GCs damage in mice. In this study, we employed iTRAQ-based proteomics to investigate the mechanism underlying the restorative effects of Scu in this model. Compared to the model group, we identified 415 differentially expressed proteins (DEPs) in both the control and Scu-treated groups, and found that these were enriched mainly in the biosynthesis and metabolism, drug metabolism, and pentose phosphate pathway. Moreover, the MAPK and heat shock protein-necroptosis pathway were implicated in regulating ZEA toxicity and the protective effect of Scu. Receptor-interacting serine threonine-protein kinase 1 (RIPK1) showed the highest fold-change in expression in the Scu-treated group. Small-interfering RNA-mediated RIPK1 knockdown further promoted the increase in cleaved-caspase-3 expression induced by ZEA, but not in the cells treated with Scu. These data indicated the involvement of multiple targets and pathways in the protective effect of Scu against ZEA-induced damage. Our findings also indicated that RIPK1 may be involved in the inhibition of GCs apoptosis induced by ZEA.
摘要：
玉米赤霉烯酮(ZEA),镰刀菌产生的一种霉菌毒素，可通过靶向卵巢颗粒细胞（GC）引起生殖障碍。我们先前表明，灯盏乙素（Scu）可以挽救ZEA诱导的小鼠GCs损伤。在这项研究中,我们采用基于iTRAQ的蛋白质组学研究了该模型中Scu恢复作用的潜在机制.与模型组相比，我们在对照组和Scu处理组中鉴定出415种差异表达蛋白（DEP），发现这些主要富集在生物合成和代谢中，药物代谢，和磷酸戊糖途径。此外，MAPK和热休克蛋白-坏死途径参与调节ZEA的毒性和Scu的保护作用。受体相互作用的丝氨酸苏氨酸蛋白激酶1（RIPK1）在Scu处理组中的表达变化倍数最高。小干扰RNA介导的RIPK1敲低进一步促进了ZEA诱导的cleaved-caspase-3表达的增加，但不是在用Scu治疗的细胞中。这些数据表明，Scu对ZEA诱导的损伤的保护作用涉及多个靶标和途径。我们的发现还表明，RIPK1可能参与抑制ZEA诱导的GCs凋亡。
