School of Basic Medicine, Ningxia Medical University, 1160 Shengli South Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, China.
School of Basic Medicine, Ningxia Medical University, 1160 Shengli South Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, China.
Gene. 2022 Aug 5;834:146565. doi: 10.1016/j.gene.2022.146565. Epub 2022 May 13.
Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor-1α (HIF-1α) are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-1α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear.
We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms.
The results show that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif1a and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α.
These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.
缺氧是诱导心肌细胞损伤的主要因素，其显著标志是缺氧诱导的心肌细胞凋亡。核呼吸因子-1（NRF-1）和缺氧诱导因子-1α（HIF-1α）是参与多种生物学功能的转录调节因子，包括氧化应激反应。然而，它们在缺氧诱导的心肌细胞凋亡中的作用尚不清楚。HIF-1α与 NRF-1 共同对心肌细胞凋亡的影响也不清楚。
我们建立了心肌缺氧模型，研究了这些蛋白在缺氧条件下对大鼠心肌细胞（H9C2）增殖和凋亡的影响。进一步研究了 NRF-1 和 HIF-1α 之间的关系，以提高对 NRF-1 抗凋亡机制的认识。
结果表明，NRF-1 和 HIF-1α 是缺氧条件下 H9C2 细胞中重要的抗凋亡分子，尽管它们的调节机制不同。NRF-1 可以与 Hif1a 的启动子区域结合，负向调节其表达。此外，HIF-1β 与 NRF-1 和 HIF-1α 表现出竞争结合，表明 NRF-1 与过氧化物酶体增殖物激活受体-γ辅激活因子-1α之间存在协同作用。
这些结果表明，心肌细胞可以调节不同的分子模式来耐受缺氧，为研究缺氧下心肌细胞凋亡提供了新的方法学框架。
