帕尔米酸诱导了热囊细胞的综合应激反应和脂质亡
Prakash Kumar Sahoo1, Chandan Krishnamoorthy1, Jennifer R Wood2
1Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
Cell death & disease
|January 11, 2024
概括
孕产妇暴露在上会触发胎盘细胞的综合应激反应,导致细胞被编程死亡. 抑制JNK会减少这种亡,而促进压力颗粒会提高细胞存活率.
科学领域:
- 生殖生物学和发育毒理学.
- 细胞应激反应机制 细胞应激反应机制
- 在子宫内代谢编程.
背景情况:
- 孕产妇的肥胖是儿童肥胖和代谢综合征的重要危险因素.
- 棕酸是一种和的自由脂肪酸 (FFA),穿过胎盘,并与胎儿编程有关.
- 之前的研究表明,母亲的和FFA诱导了 trofhoblast lipoapoptosis.
研究的目的:
- 调查palmitate是否会诱导热囊细胞的综合应激反应通路.
- 确定基激活蛋白激酶 (MAPKs),内细胞网膜 (ER) 应激和颗粒性应激在棕酸盐诱导的热细胞脂质亡中的作用.
- 为了阐明涉及到palmitate诱导的热囊细胞死亡的机制性途径.
主要方法:
- 对JEG-3和JAR热囊细胞暴露于不同度的棕酸盐 (PA).
- 通过核形态学和caspase 3/7活动评估亡.
- 免疫斑块和免疫光分析以检测MAPK,ER压力和压力颗粒激活;评估CHOP和FoxO3的核转移.
主要成果:
- 暴露在Palmitate中引起了由卡斯巴酶3/7.7介导的热囊细胞脂亡的度依赖性增加.
- 棕酸激活了MAPKs (JNK,ERK) 和ER压力 (eIF2α,IRE1α酸化),并诱导了压力颗粒的形成.
- 基激活对PA诱导的多细胞脂肪亡至关重要,而ERK激活和压力颗粒形成则充当细胞生存信号.
结论:
- 棕酸会触发热囊细胞的综合应激反应,包括MAPK和ER应激通路.
- 在Palmitate诱导的热囊细胞死亡中,JNK激活是必不可少的.
- 增强压力颗粒的形成可以保护热囊细胞免受Palmitate诱导的脂质亡.
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