一个酸性pH值环境将死细胞亡转化为死细胞亡
Haitao Lu1, Laura Xu1, Julia Steriopoulos1
1Matthew Mailing Centre for Translational Transplantation Studies. Lawson Health Research Institute, London, Canada; Department of Pathology, Western University, London, Canada.
Biochemical and biophysical research communications
|June 13, 2024
概括
酸化通过改变RIPK1/3和MLKL活动,将心脏细胞死亡从死转移到亡. 这种依赖pH值的开关突出显示了诱导亡的因素.
科学领域:
- 心血管生物学 心血管生物学
- 细胞死亡机制 细胞死亡机制
- 生物化学 生物化学
背景情况:
- 心脏缺血诱导酸性,有助于编程细胞死亡和恶化心脏功能.
- 亡,一种主要的编程亡形式,加剧心脏功能障碍和炎症.
- 酸化对特定编程细胞死亡途径,特别是亡的影响仍然不太清楚.
研究的目的:
- 为了研究酸性微环境pH对心脏细胞编程细胞死亡途径的影响.
- 阐明在不同pH条件下死媒介 (RIPK1/3,MLKL) 和死诱导因子 (AIF) 的作用.
主要方法:
- 在生理 (pH 7.4) 和酸性 (pH 6.5) 条件下用TNFα治疗小鼠心血管内皮细胞 (MVEC).
- 抑制caspase-8和RIPK1以评估它们在TNFα诱导的细胞死亡中的作用.
- 分析死细胞分子酸化 (RIPK1,RIPK3,MLKL) 和诱导亡因子 (AIF) 裂变和转移.
主要成果:
- 在pH7.4时,TNFα诱导的亡,由RIPK1抑制阻断细胞死亡证实.
- 在pH 6.5时,TNFα诱导了类似于细胞亡的细胞死亡,对caspase-8抑制敏感.
- 酸性pH增强了RIPK1,RIPK3和MLKL的酸化,但限制了RIPK3/MLKL的活性,同时促进了AIF分裂和核转移,这对细胞死亡至关重要.
结论:
- 微环境的pH显著影响心脏细胞中被编程的细胞死亡途径.
- 酸化促进了AIF介导的亡,同时可能限制了亡.
- 了解这些依赖pH值的机制可能为缺血-再输液损伤提供新的治疗点.
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