血清饥饿通过HIF-1激活和JNK抑制诱导密度依赖的亡
Qifan Yang1, Yaofeng Hu1, Jiahui Lv1
1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Acta biochimica et biophysica Sinica
|November 14, 2025
概括
血清饥饿会通过激活HIF-1α和抑制JNK信号来触发高密度细胞中的细胞死亡 (细胞灭亡). 这种密度依赖的开关促进了代谢应激适应和细胞生存向.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 血清剥夺是已知亡的触发因素之一.
- 血清剥夺诱导的亡背后的精确分子机制尚未完全理解.
- 细胞密度在细胞对压力的反应中起作用.
研究的目的:
- 阐明血清饥饿以密度依赖的方式诱导亡的分子机制.
- 研究HIF-1α和JNK信号在这个过程中的作用.
- 为了确定营养应激诱导的亡的关键调节者.
主要方法:
- 使用了高密度和低密度的小鼠胚胎纤维细胞 (MEF).
- 执行了HIF-1α的基因淘汰.
- 分析了caspase-3激活和JNK通路活性.
- 在低密度细胞中操纵HIF-1α表达和JNK信号.
主要成果:
- 血清饥饿在高密度MEF中选择性诱导内在亡.
- 对于这种反应,HIF-1α激活和JNK信号抑制至关重要.
- HIF-1α敲击消除了血清剥夺诱导的亡.
- 在低密度细胞中HIF-1α的升级模仿了高密度细胞灭绝.
- 抑制JNK通路有助于细胞亡.
- 在低密度细胞中,HIF-1α激活和JNK抑制的结合完全复制了高密度细胞灭亡.
结论:
- 一个密度依赖的亡开关是由HIF-1α激活和JNK抑制调节的.
- HIF-1α促进了代谢应激适应,而JNK抑制则消除了生存信号.
- 这些途径汇聚在一起,诱导线粒体介导的细胞死亡.
- 为营养应激诱导的亡提供了一个机制框架.
- 表明异常细胞存活率的疾病的潜在治疗点.
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