通过抑制LEC中的P53通路,APEX1减轻了ERS诱导的亡
Renhao Zhong1, Lihua Kang1, Wenjing Geng1
1Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Experimental eye research
|April 20, 2025
概括
与年龄相关的皮质白内障包括真空孔和状的不透明度. 细胞中的APEX1蛋白过度表达通过调节P53和ATF6减弱了亡,这表明了白内障的新治疗.
科学领域:
- 眼科医生 眼科 眼科
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 与年龄相关的皮质白内障 (ARCC) 的特点是空隙和类似的不透明性.
- 帕拉普托斯是一种编程细胞死亡形式,与早期ARCC真空性退化有关.
- 了解ARCC背后的分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 研究APEX1在过氧化 (H2O2) 诱导的类似亡的细胞模型中的作用和机制.
- 探索APEX1,内细胞网膜 (ER) 应激和ARCC中的亡之间的关系.
- 为了确定ARCC的潜在治疗点.
主要方法:
- 通过使用H2O2诱导的SRA01/04细胞建立了类似亡的细胞模型.
- 利用定量逆转录聚合酶链反应 (qRT-PCR) 和西布洛特分析基因和蛋白质表达.
- 采用共聚焦光显微镜,共免疫沉 (co-IP),GTRD数据库分析和CUT&RUN测试来阐明分子相互作用和途径.
主要成果:
- ARCC患者的透镜截面显示了纤维混乱和真空球的发展,H2O2处理的细胞中的Alix蛋白表达减少.
- 过度表达APEX1改善了ER形态,减少了P53-ATF6相互作用,并在SRA01/04细胞中减弱了亡.
- APEX1调节了P53,这反过来又调节了ATF6,影响了ER压力和亡.
结论:
- 在SRA01/04细胞中,APEX1对H2O2诱导的亡起着保护作用.
- 该机制涉及APEX1调节P53以调节ATF6,从而影响ER压力和亡.
- APEX1是缓解与年龄相关的皮质白内障进展的潜在治疗标.
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