数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
The endoplasmic reticulum (ER) stress response is a compartmentalized form of the cellular stress response that usually involves the sensing of unfolded/misfolded proteins in the ER lumen, followed by the processing and transmission of this information to the nucleus and other cellular compartments [1,2].
方法
Cell Cultures and Senescence Induct] The Jurkat cell line was obtained from the Russian Cell Culture Collection (Institute of Cytology, Russian Academy of Sciences, Saint Petersburg, Russia) and maintained in RPMI-1640 medium (Life Technologies, Grand Island, NY, USA) supplemented with 10% (v/v) fetal bovine serum (FBS; Life Technologies, Grand Island, NY, USA) and 50 µg/mL gentamicin (Life Technologies).;Edgell (University of North Carolina, Chapel Hill, NC, USA) and cultured in Dulbecco’s Modified Eagle’s Medium (DMEM; Life Technologies) supplemented with 10% (v/v) FBS, 1% non-essential amino acids (Paneko, Moscow, Russia), 2 mM glutamine (Paneko), HAT supplement (Life Technologies), and 50 µg/mL gentamicin.;Experimental Treatments] To induce ER stress, cells were treated with various concentrations of dithiothreitol (DTT; Sigma-Aldrich, St.;Cells were pre-incubated with the inhibitor STF 083010 at a final concentration of 60 µM before ER stress induction.
核心结论
When comparing the expression levels of individual key genes, we observed 6-fold higher expression of SEC61A1, a core translocon component; a 56-fold increase in CKAP4 (CLIMP-63), which anchors the ER to microtubules; and an 11-fold elevation in HSPA5 (BiP), the primary ER chaperone.;Specifically, we noted divergent expression of reticulons, which stabilize ER membrane curvature: RTN2 expression was upregulated 39-fold, which may reflect active secretory traffic, while RTN4 showed a 2.4-fold increase, suggesting a moderate expansion of the tubular ER in EA.hy926 cells.;In EA.hy926 cells, ATF6 expression was 1.6-fold higher, concurrently with its target genes SEL1L (an ERAD-associated protein component) and HERPUD1, which showed 1.3-fold and 2-fold increases, respectively. ‖ 结论:We demonstrate that UPR dynamics are significantly modulated by cellular geometry.
局限
Nevertheless, the temporal dynamics of ER stress induced by alternative agents may exhibit unique cell type-specific features, which warrant further investigation.
对本项目的价值
★★☆☆☆ 细胞衰老清除/重编程是项目干预管线的核心支柱之一。设计 多组学、定性研究。
全文来源
PMC JATS 全文(正文 54,005 字符,已过标题/DOI 逐字归属校验)
原文题录
- 英文标题:Dynamics of Endoplasmic Reticulum Stress Responses in Cells with Different Endoplasmic Reticulum Volumes and Senescence States.
- 期刊与标识:Curr Issues Mol Biol · PMID 42939565 · DOI 10.3390/cimb48101027**
B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)
本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。
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