在低氧的情况下,MYC取代HIF-1α来调节增殖的初级细胞代谢
Courtney A Copeland1,2, Benjamin A Olenchock1,2, David Ziehr1,2,3
1Department of Medicine, Brigham and Women's Hospital, Boston, United States.
eLife
|July 10, 2023
概括
缺氧令人惊地减少了肺细胞中的细胞糖解,尽管激活了缺氧诱导因子1α (HIF-1α). 似乎MYC信号将HIF-1α脱.
科学领域:
- 细胞代谢的细胞代谢.
- 缺氧的研究研究缺氧.
- 分子生物学分子生物学
背景情况:
- 在低氧条件下,代谢适应对细胞生存至关重要.
- 虽然癌细胞得到了充分的研究,但对原发性细胞对缺氧的反应仍然不太了解.
- 低氧诱导因子1α (HIF-1α) 是细胞对低氧反应的关键调节者.
研究的目的:
- 在低氧条件下研究人类初级肺细胞的代谢流.
- 阐明HIF-1α和MYC在低氧期间调节细胞代谢中的作用.
- 为了比较对低氧的分子反应与酸酶 (PHD) 抑制的分子反应.
主要方法:
- 开发人类肺纤维细胞和肺动脉光滑肌细胞的代谢流量模型.
- 多原子分析分析分析分子变化.
- 基因操纵 (敲击和过度表达) 来评估MYC.的作用.
主要成果:
- 低氧会降低肺细胞中的糖分解,与预期相反,尽管HIF-1α激活和增加了糖分解酶表达.
- 在normoxia中抑制基酶 (PHD) 会增加葡萄糖分解,这种效应被缺氧阻断.
- 确定MYC信号作为一个关键因素,将HIF-1α转录活性从糖溶性流量中解离.
结论:
- 在初级肺细胞中,MYC在调节HIF-1α对低氧反应方面发挥着关键作用.
- 缺氧诱导的MYC信号扰乱了预期的糖解增加.
- 这些发现揭示了一种新的机制,通过该机制在低氧条件下调节细胞代谢.
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