肠上皮细胞中紧密结合的破坏,由有毒的高级糖化最终产品引起的
Ryoma Takeda1, Eisei Hori1, Misaki Natori2
1Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
糖衍生有毒的先进糖化终产物 (TAGE) 通过破坏上皮细胞和减少紧密结合蛋白来破坏肠道屏障功能. 这导致透性增加和细胞死亡,突出了肠道屏障破坏的新机制.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 肠上皮细胞 (IECs) 形成了一个重要的屏障,其破坏与炎症性肠病有关.
- 甘 (GA) 衍生的高级糖化终产物 (AGEs),特别是有毒的AGEs (TAGE),与屏障功能障碍有关,但机制尚不清楚.
研究的目的:
- 研究TAGE积累对肠上皮质屏障功能的影响,重点关注Caco-2细胞的紧密结节.
- 阐明TAGE诱导的肠壁破坏背后的分子机制.
主要方法:
- 卡科-2细胞被GA治疗以诱导细胞内TAGE的形成.
- 免疫光染色被用于评估紧结蛋白 (ZO-1,claudin-7).
- 评估了反应性氧物种 (ROS) 生产和NAD(P) H氧化酶基因表达.
主要成果:
- GA治疗增加了细胞内TAGE,导致细胞死亡和增加了细胞透性.
- GA降低了紧结蛋白ZO-1和claudin-7的表达.
- 在GA治疗的细胞中观察到过度的ROS产生和增加的NAD(P) H氧化酶基因表达,表明细胞毒性和亡.
结论:
- TAGE诱导通过细胞损伤破坏肠道上皮质紧密结节.
- 这一过程涉及ROS的产量增加和细胞毒性,有助于肠道屏障的破坏.
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