DEK 与 IRE1α 相互作用,以调节脱氧尼瓦诺醇诱导的肠炎症中的内分泌网膜应激
Lingjie Zeng1,2,3, Danni Yu1,3, Jintao Xu1,3
1State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, Guangdong, P. R. China.
Journal of agricultural and food chemistry
|August 13, 2025
概括
脱氧尼瓦伦醇 (DON) 菌毒素通过向DEK蛋白来损害肠道,破坏了内分泌网膜 (ER) 的压力调节. 恢复DEK功能可能会防止DON引起的肠损伤.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 脱氧尼瓦伦醇 (DON) 是一种普遍存在的真菌毒素,可引起显著的肠道损伤.
- 导致DON引起的肠损伤的精确分子机制尚未完全理解.
- 细胞内膜网膜 (ER) 的压力与DON毒性有关.
研究的目的:
- 为了确定DON在肠道损伤中的关键分子点.
- 阐明DEK蛋白在DON引起的ER压力和炎症中的作用.
- 在DON毒性背景下研究DEK-IRE1α相互作用.
主要方法:
- 使用肠道细胞进行体外研究,以评估DON-DEK-IRE1α相互作用.
- 结构分析以确定关键的结合残留物.
- 基因操纵 (过度表达和淘汰) 来评估DEK功能.
- 在暴露于DON的小鼠和小猪身上进行了体内研究.
主要成果:
- 在特定的残留物 (Phe56,Lys68,Leu106) 上,DON直接与DEK蛋白结合.
- DON破坏了DEK和IRE1α之间的相互作用,这是一个关键的ER压力调节器.
- DEK的过度表达减轻了DON引起的ER压力和炎症;DEK的倒退加剧了它.
- 在体内暴露于DON会导致肠道损伤和DEK依赖的ER压力.
结论:
- 一个新的DEK-IRE1α轴被确定为在DON毒性中至关重要的.
- DEK通过调节ER压力,对DON引起的肠损伤起着保护作用.
- DEK代表了预防或治疗DON引起的肠损伤的潜在治疗标.
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