IP3R介导的释放促进了SH-SY5Y神经母细胞瘤细胞中的ferroptotic死亡
Joaquín Campos1, Silvia Gleitze2, Cecilia Hidalgo2,3,4
1Chica and Heinz Schaller Foundation, Institute for Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany.
Antioxidants (Basel, Switzerland)
|February 24, 2024
概括
铁,一种依赖于铁的细胞死亡,涉及SH-SY5Y细胞通过IP3R通道释放. 抑制GPx4会触发这种情况,增加,ROS和脂质过氧化,最终导致细胞死亡.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 铁亡是一种依赖于铁的细胞死亡途径,其特征是谷氨耗尽和脂质过氧化.
- 抑制谷氨过氧化酶4 (GPx4) 是已知的铁灭症诱导剂.
- 通过氨酸受体 (RyRs) 从内质网膜 (ER) 释放的与神经元中的铁亡有关.
研究的目的:
- 研究伊诺西1,4,5-三酸盐受体 (IP3R) 通道在铁灭菌诱导的细胞死亡中的作用.
- 确定IP3R介导的释放是否有助于SH-SY5Y神经母细胞瘤细胞的铁亡,这些细胞缺乏RyR通道.
主要方法:
- 用RSL3,一种GPx4抑制剂治疗SH-SY5Y细胞.
- 通过使用Xestospongin B或carbachol抑制IP3R通道.
- IP3R1表达式的淘汰. 这是IP3R1表达式的淘汰.
- 用BAPTA-AM进行细胞内化.
- 评估活性氧物种 (ROS) 生成,细胞质和线粒体水平,脂质过氧化和细胞形态.
主要成果:
- RSL3治疗诱导了铁亡,由增加的ROS,水平和脂质过氧化证明.
- 抑制IP3R通道 (使用Xestospongin B,carbachol或IP3R1淘汰) 显著降低RSL3诱导的信号,并防止细胞死亡和形态变化.
- RSL3诱导的信号取决于细胞内的释放,而不是细胞外.
结论:
- 抑制GPx4激活了SH-SY5Y细胞中的IP3R介导的从ER释放.
- 这种释放增加了细胞质和线粒体的,刺激ROS的产生和脂质过氧化.
- 一个积极的反循环,涉及IP3R介导的释放,有助于ferroptosis执行.
关键词:
在RSL3中使用RSL3.信号传递的.细胞死亡是细胞死亡.细胞内膜网膜的内oplasmic网膜.铁性化 (ferroptosis) 是一种谷氨过氧化酶的使用方法脂类过氧化过氧化氧化应激是一种氧化应激.有活性氧物种的反应性氧物种.更多相关视频
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