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曼吉费林通过SIRT1激活保护介酶干细胞免受DNA损伤和细胞衰老
Gyeong Min Lim1, Gwang-Won Cho2
1Department of Biological Science, College of Natural Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea; BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Republic of Korea.
Mechanisms of ageing and development
|January 28, 2025
概括
曼吉费林 (MAG) 保护人类骨髓中介质干细胞 (hBM-MSCs) 免受埃托和高葡萄糖引起的DNA损伤和衰老. MAG激活关键蛋白质,保持基因组稳定性并减少衰老标志物.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 老年学是一门学科.
背景情况:
- DNA损伤和细胞衰老与各种疾病有关.
- 介质干细胞 (MSC) 容易受到基因毒性压力和衰老的影响.
- 高葡萄糖 (HG) 条件可以加剧细胞损伤和衰老过程.
研究的目的:
- 调查曼吉费林 (MAG) 对人类骨髓-介质干细胞 (hBM-MSCs) 中的乙酸和HG诱导的DNA损伤和衰老的保护作用.
- 阐明MAG的保护作用背后的分子机制.
主要方法:
- 使用埃托波西德 (一种拓酶II抑制剂) 诱导DNA损伤,并长期暴露于高葡萄糖 (HG).
- 对DNA损伤标志物的评估 (例如,γ-H2AX焦点,双链断裂 (DSB),基因毒性和衰老标志物 (例如,H3,H4,LMNB1,CDKN1A,CDKN2A,p53).
- 对关键信号通路 (AMPK,SIRT1) 和表观遗传修饰 (LINE1,TRIM28,H3K9me3) 的分析.
- 对细胞增殖和老化相关的分泌表型 (SASP) 因素的评估.
主要成果:
- 通过激活AMPK和SIRT1.1,MAG保护了hBM-MSCs免受埃托胺诱导的DSBs的影响.
- MAG减轻了HG诱导的DNA损伤,并延迟了细胞衰老,保持了关键的结构和mRNA水平.
- 通过减少LINE1表达和保持异色染色素标记物,MAG增强了基因组稳定性.
- MAG和甲福林治疗改善了细胞增殖,减少了衰老标志物,并减少了SASP因子的释放.
结论:
- 曼吉费林在基因毒性和高葡萄糖压力下显示出对hBM-MSCs的DNA损伤和衰老具有显著的保护作用.
- MAG的机制包括激活AMPK/SIRT1通路,增强基因组稳定性和减少衰老.
- 曼吉费林具有作为治疗与衰老相关的疾病和与DNA损伤相关的疾病的治疗剂的潜力.
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