与青光眼相关的多态性M98K-OPTN通过p62-介导的caspase激活使视网膜细胞对蛋白质稳态应激敏感
Swetha Medchalmi1, Zuberwasim Sayyad1, Ghanshyam Swarup1
1CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.
Biochimica et biophysica acta. Molecular cell research
|September 26, 2025
概括
在OPTN中的M98K多态可能会增加视网膜细胞对蛋白质应激的脆弱性. 这种变异增强了细胞死亡信号,可能与其他因素一起导致青光眼的发展.
科学领域:
- 眼科医生 眼科 眼科
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 在一些人群中,Optineurin (OPTN) 的M98K多态性与玻璃眼有关.
- 玻璃眼引起的视力丧失源于视网膜质细胞退化.
- M98K-OPTN变异在青光眼病原体中的作用尚不清楚,可能需要辅助因子.
研究的目的:
- 调查M98K-OPTN是否增强视网膜细胞对蛋白质稳态应激的敏感性.
- 阐明M98K-OPTN在青光眼中潜在作用的分子机制.
主要方法:
- 使用了表达视网膜661W细胞克隆的M98K-OPTN和野生型 (WT) -OPTN.
- 使用蛋白质酶抑制剂MG132.2诱导的蛋白质稳态应激.
- 评估了细胞存活率,酶激活 (酶-8, -9, -3) 和p62/SQSTM1聚合物形成.
主要成果:
- 与WT-OPTN细胞相比,M98K-OPTN表达细胞在压力下表现出降低的生存率和增加的酶激活.
- 在压力期间,M98K-OPTN细胞显示了增强的p62/SQSTM1聚合物形成和蛋白质水平.
- 在暴露于蛋白酶抑制的M98K-OPTN细胞中,p62敲击减轻了酶激活.
结论:
- M98K-OPTN表达使视网膜细胞对蛋白质平衡应激敏感.
- 这种敏感性涉及酶激活通路的p62-依赖调制.
- M98K-OPTN变异可能通过增加视网膜细胞对蛋白质毒性压力的敏感性,从而导致青光眼.
关键词:
眼光障碍 眼光障碍 眼光障碍 眼光障碍神经退行发生神经退行.选择性尿素 (Optineurin) 是一种可视化尿素.蛋白质聚合蛋白质的聚合.蛋白质平衡压力是蛋白质平衡的压力.p62/SQSTM1 一个问题.更多相关视频
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