DDIT4/mTOR信号通路介导着利丁诱导的肝毒性和细胞损伤
Wenchao Tang1, Yue Pan1, Can Zhu1
1School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Frontiers in pharmacology
|November 20, 2024
概括
坎塔里丁 (CTD) 通过激活DDIT4/mTOR通路而导致肝损伤,增加了自和亡. 抑制DDIT4可以降低CTD毒性,而增强DDIT4则会使损伤恶化.
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:
- 康达里丁 (CTD) 来自传统中医药,显示出抗瘤的潜力.
- CTD的高毒性会导致严重的肝损伤,其分子机制尚不清楚.
研究的目的:
- 阐明CTD诱导的肝毒性背后的分子机制.
- 调查DNA损伤诱导的转录因子4 (DDIT4) 在CTD毒性的作用.
主要方法:
- 已建立的小鼠模型和L-O2细胞培养物用于CTD诱导的肝损伤.
- 分析肝功能,病理和细胞活动 (CCK-8测定).
- 量化DDIT4,自和亡标志物使用qPCR,西式涂抹和显微镜.
主要成果:
- 暴露于CTD会导致严重的肝损伤,并降低L-O2细胞活力.
- CTD增加了DDIT4,LC3-II,Beclin1和Bax,同时降低了p-mTOR和Bcl-2.
- DDIT4干扰和3-MA降低了CTD诱导的自和亡;Rap治疗增强了它们.
结论:
- 由CTD引起的肝毒性涉及DDIT4/mTOR通路的激活.
- 这一途径导致肝细胞中自和亡的增加.
- 准DDIT4可能为CTD诱导的肝损伤提供治疗策略.
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