JNK分子是IPEC-J2细胞屏障损伤的有毒标,由T-2毒素诱导
Fengjuan Chen1, Youshuang Wang1, Yunhe Chen1
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002 Henan, China.
Ecotoxicology and environmental safety
|July 15, 2023
概括
通过激活JNK分子,T-2毒素会破坏肠道细胞,导致氧化应激和炎症. 抑制JNK可以保护肠道上皮细胞免受T-2毒素引起的伤害.
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:
- T-2毒素是料和谷物中普遍存在的真菌毒素.
- 它主要针对肠道,通过基本上未知的分子机制引起肠道损伤.
- 了解这些途径对于解决T-2毒素肠毒性至关重要.
研究的目的:
- 研究MAPK信号通路在T-2毒素引起的肠上皮细胞损伤中的作用.
- 使用IPEC-J2细胞阐明T-2毒素肠毒性背后的分子机制.
主要方法:
- 利用IPEC-J2细胞作为肠道上皮细胞的模型.
- 评估T-2毒素对细胞活力,LDH释放,紧结蛋白表达,氧化应激标志物 (ROS,MDA),线粒体功能 (MMP,MPTP) 和炎症因素 (IL-8,p65,P-p65,IL-6,IL-10) 的影响.
- 研究了MAPK信号通路 (ERK,P38,JNK) 的激活以及JNK抑制的影响.
主要成果:
- T-2毒素通过减少紧密结蛋白 (Claudin,Occludin-1,ZO-1,N-cadherin,CX-43) 来降低IPEC-J2细胞功能的受损.
- T-2毒素降低了细胞存活率,并以剂量依赖的方式增加了LDH释放.
- 它诱导了氧化应激 (增加ROS,MDA) 和线粒体损伤 (减少MMP,增加MPTP开放).
- 通过对ERK,P38和JNK进行上调,T-2毒素激活了MAPK通路.
- 引发了炎症反应,增加了IL-8,p65,P-p65,IL-6,并减少了IL-10.
- 抑制JNK缓解了细胞功能障碍和炎症反应.
结论:
- T-2毒素激活了MAPK信号通路中的JNK分子.
- 这种激活导致氧化应激和线粒体损伤,导致肠道上皮细胞损伤.
- 抑制JNK提供了一种潜在的治疗策略,以减轻T-2毒素引起的肠毒性和炎症.
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