介质组成和氧气压力对细胞应激反应和HepG2ARE细胞中Nrf2激活的影响
Rutt Taba1, Marie Põlluaed1, Karin Tein1
1Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia.
Antioxidants (Basel, Switzerland)
|February 26, 2025
概括
细胞培养基和氧气水平显著影响细胞应激反应和Nrf2激活. 优化这些条件对于准确的体外疾病建模和药物发现至关重要.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 临床前研究 临床前研究
背景情况:
- 在体外细胞模型对于理解疾病机制和药物发现至关重要.
- 标准的细胞培养条件往往忽略了营养素和氧气水平对细胞反应的影响.
- 细胞应激通路对微环境敏感,包括营养物质的可用性和氧气张力.
研究的目的:
- 研究如何用等离子体样介质 (Plasmax) 代替标准细胞介质 (DMEM) 影响细胞活力和压力标志物.
- 评估环境 (~19%) 与降低 (5%) 氧气水平对细胞反应的影响.
- 确定生长条件对核红色素2相关因子2 (Nrf2) 的激活以及谷氨酸 (GSH) 和氨酸 (MDA) 的水平的影响.
主要方法:
- 在环境或减少氧气条件下,在DMEM或Plasmax介质中培养HepG2ARE细胞.
- 细胞接受了细胞应激的药理诱导剂的治疗,包括铁灭激活剂 (erastin,RSL3) 和内分泌网膜应激诱导剂 (thapsigargin).
- 测量了细胞活力,Nrf2激活,GSH和MDA水平,以评估细胞反应.
主要成果:
- 铁致死诱导剂的Nrf2激活因细胞介质和氧气张力而异.
- 只在低氧时的DMEM中观察到Thapsigargin诱导的Nrf2激活.
- 血介质导致GSH和MDA水平升高,表明细胞氧化还原状态发生变化.
结论:
- 细胞应激耐受性和Nrf2激活受细胞介质组成和HepG2ARE细胞中的氧气张力显著影响.
- 由于标准的细胞培养实践,当前的体外模型可能无法准确地反映体内条件.
- 仔细考虑细胞培养条件对于开发可靠的体外模型至关重要,特别是在涉及氧化应激的疾病中.
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