在人体胆瘤细胞中诱导PERK-ATF4无折叠蛋白反应和亡
Josianne Bienvenue-Pariseault1,2, Lucas Sagrillo-Fagundes1,2, Philippe Wong-Yen1
1Institut national de la recherche scientifique (INRS) - Centre Armand-Frappier Santé Biotechnologie (AFSB), Laval, Canada.
Journal of pineal research
|August 28, 2025
概括
通过激活PERK-ATF4-CHOP通路,这是未折叠蛋白质反应的关键组成部分,以诱导胆瘤细胞的亡. 这突出了黑色素
科学领域:
- 癌症学
- 分子生物学
- 细胞生物学
背景情况:
- 一种调节昼夜节律的荷尔蒙 - - 氨酸, 在各种癌症中具有抗瘤作用.
- 黑色素诱导细胞亡并降低胎盘胆瘤细胞的活力,部分是通过抑制自.
- 黑素在内分泌网膜 (ER) 应激和未折叠蛋白质响应 (UPR) 途径中的作用尚不清楚.
研究的目的:
- 通过激活 UPR 途径来调解黑素在胆癌细胞中的前性作用的假设.
- 阐明在BeWo细胞中参与黑激素诱导的特定UPR信号组件.
主要方法:
- 人类胆瘤 BeWo 细胞用黑素 (1 mM) 进行治疗.
- 使用西部斑块和RT- qPCR分析了UPR因子 (PERK,IRE1α,ATF6,GRP78,ATF4,CHOP,P- eIF2α,TRAF2,NFkB) 的蛋白质和mRNA水平.
- 使用流细胞计量来评估早期细胞亡以及PERK敲除 (siRNA) 对突尼卡米辛诱导的ER压力下的细胞存活的影响.
主要成果:
- 黑素显著增加了GRP78,IRE1α,p-eIF2α,ATF4,CHOP,Bax和分裂的PARP的蛋白质水平.
- 消除了美拉激素引起的GRP78,p-eIF2α/ eIF2α和ATF4的增加.
- 黑素促进了BeWo细胞的早期亡,而PERK缺陷使细胞对基胺诱导的亡敏感,这表明ER应激在细胞存活中的作用.
结论:
- 黑色素激活PERK-ATF4-P-eIF2α-CHOP信号通路,导致人类胆瘤BeWo细胞的亡.
- 在ER压力下,PERK-UPR途径在BeWo细胞生存中发挥着关键作用.
- 用黑素准PERK- UPR信号通路为胎盘胆瘤和其他癌症提供了潜在的治疗策略.
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