长期的HIF-1α稳定会减少呼吸,促进细胞和导致视网膜细胞死亡
Nana Yaa Nsiah1,2, Autumn B Morgan1, Nina Donkor1
1Department of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA.
Scientific reports
|November 23, 2023
概括
低氧诱导因子1-α (HIF-1α) 的慢性激活会引发代谢变化和视网膜细胞死亡,这表明它可以独立于高眼压驱动青光眼病理.
科学领域:
- 眼科医生 眼科 眼科
- 代谢途径 代谢途径
- 细胞生物学 细胞生物学
背景情况:
- 玻璃眼和眼睛高血压可能导致缺氧,导致HIF转录因子的激活和代谢转移到糖解.
- 这种新陈代谢重编程可能会导致与玻璃眼相关的病理.
研究的目的:
- 调查慢性HIF激活是否可以独立于眼睛高血压,启动与青光眼相关的病理.
- 分析持续在视网膜中稳定HIF-1α的代谢和细胞后果.
主要方法:
- 在小鼠中诱导HIF-1α稳定,使用prolyl氧酶抑制剂Roxadustat2周和4周.
- 用免疫光,毛细血管电泳和酶活性测试来评估视网膜变化.
- 细胞亡和视网膜质细胞功能通过TUNEL测定和PERG振幅进行了评估.
主要成果:
- 罗沙杜沙特治疗稳定了HIF-1α,上调了糖解相关蛋白质 (GLUT3,PDK-1) 和酶活性.
- 线粒体标志物 (SDH,MTCO1,酸盐合成酶) 降低,而线粒体菌增加.
- 观察到显著的视网膜细胞亡,PERG振幅下降,AMPK激活增加和质缩.
结论:
- 仅仅慢性HIF-1α稳定对视网膜代谢平衡和细胞存活是有害的.
- 这些发现表明,HIF-1α激活可以独立于眼睛高血压驱动青光眼病理.
- 由HIF-1α诱导的代谢重编程有助于视网膜细胞死亡和功能障碍.
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