Hippo-YAP信号通过ATOX1-PPA2通路缓解铜诱导的线粒体功能障碍和氧化损伤
Hai-Fan Yu1, Qi-Ran Zeng1, Pengyu Xiao1
1Laboratory of Animal Developmental Biology, College of Life Science, Northeast Forestry University, Harbin 150040, China.
International journal of biological macromolecules
|December 20, 2024
概括
通过恢复线粒体功能,Hippo-YAP信号保护抗铜应激. 这一途径通过ATOX1和PPA2.2,增强抗氧化能力和细胞铜平衡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 河马信号对于细胞应激反应至关重要.
- 它在铜 (Cu) 应力中的作用在很大程度上是未知的.
- 过量的会导致胰腺损伤和氧化应激.
研究的目的:
- 调查Cu诱导的胰腺损伤中的Hippo-YAP信号.
- 阐明Cu恒温调节的分子机制.
- 确定向这种途径的治疗潜力.
主要方法:
- 绵羊胰腺和有机体模型接触过多的Cu.
- 对Hippo-YAP通路激活及其下游目标的分析.
- 评估线粒体功能,氧化应激和Cu水平.
- 基因表达分析和蛋白质-蛋白质相互作用研究.
主要成果:
- 在暴露于Cu的绵羊胰腺和有机体中观察到异常的Hippo-YAP激活.
- 保护Hippo抑制或YAP过度表达免受Cu毒性影响.
- YAP-TEAD相互作用上调了ATOX1,恢复了线粒体功能.
- ATOX1激活了PPA2转录,增强了线粒体ATP的产生.
- 过度表达PPA2促进了Cu的流出,并恢复了细胞Cu的平衡.
结论:
- Hippo-YAP信号减轻了Cu诱导的氧化损伤和胰腺病理.
- 该途径通过ATOX1-介导的PPA2激活恢复线粒体功能.
- 这种机制确保了细胞的Cu流出,并增强了抗氧化剂防御.
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