PANX1介导的ATP释放赋予了FAM3A对肝脏葡萄糖生成和脂质生成的抑制作用
Cheng-Qing Hu1,2, Tao Hou1, Rui Xiang1
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences/State Key Laboratory of Vascular Homeostasis and Remodeling/Center for Non-Coding RNA Medicine, Peking University Health Science Center, Beijing, 100191, China.
Military Medical Research
|June 27, 2024
概括
泛素1 (PANX1) 通道释放腺三酸盐 (ATP) 调节肝脏新陈代谢. 这项研究揭示了PANX1对于家族与序列相似性3成员A (FAM3A) 控制肝脏葡萄脂平衡至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞的新陈代谢
- 肝病学 肝病学是一种肝病学.
背景情况:
- 细胞外腺三酸盐 (ATP) 作为一个关键的信号分子.
- 序列相似性3成员家族A (FAM3A) 影响肝脏葡萄脂代谢,但其促进肝细胞中ATP释放的机制尚不清楚.
研究的目的:
- 阐明FAM3A促进肝细胞中ATP释放的机制.
- 为了研究板素1 (PANX1) 在肝脏葡萄脂代谢中的作用及其与FAM3A的联系.
主要方法:
- 使用了db/db,高脂肪饮食 (HFD) 养和全球泛素1 (PANX1) 淘汰赛小鼠,以及人类肝脏样本.
- 使用病毒载体进行体内基因操纵,并进行代谢试验 (OGTT,PTT,ITT,MRI).
- 使用共免疫沉和质谱学研究了蛋白质与蛋白质相互作用.
主要成果:
- 在脂肪性肝脏中增加PANX1表达;肝脏PANX1过度表达改善了肥胖小鼠的代谢功能障碍.
- PANX1 缺乏导致葡萄糖脂代谢受损,通过恢复肝脏的 PANX1.1 来挽救.
- 确定了抑制葡萄糖生成的PANX1-激活的Akt-FOXO1通路和抑制脂质生成的PANX1-CaM-JNK-AP1通路.
- FAM3A通过HSF1刺激PANX1的表达;在PANX1缺乏的细胞和肝脏中,FAM3A的代谢益处被废除了.
结论:
- PANX1介导的ATP释放对于维持肝脏葡萄脂平衡至关重要.
- PANX1赋予FAM3A对肝脏葡萄糖生成和脂质生成的抑制作用.
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