乳酸通过与Akt相互作用,促进核脉细胞衰老和相应的椎间盘退化
Yuyao Zhang1,2, Libangxi Liu1,2,3, Yuhan Qi4
1Department of Orthopedics, Xinqiao Hospital, Army Military Medical University, Chongqing, 400037, China.
Cellular and molecular life sciences : CMLS
|January 11, 2024
概括
高乳酸水平有助于椎间盘退化 (IVDD) 通过诱导核细胞 (NPC) 衰老和氧化应激. 向乳酸可能为IVDD提供一种新的治疗方法.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 整形外科 整形外科 整形外科
背景情况:
- 椎间盘退化 (IVDD) 与代谢物积累有关.
- 乳酸是无氧糖解的产物,与IVDD有关.
- 乳酸在核细胞 (NPC) 衰老和氧化应激中的特定作用尚不清楚.
研究的目的:
- 研究乳酸对NPC衰老和氧化应激的影响.
- 为了阐明底层的分子机制.
- 探索乳酸作为IVDD的潜在治疗点.
主要方法:
- 建立了一个刺穿诱导的磁盘退化 (PIDD) 鼠标模型.
- 进行了代谢分析,以测量乳酸水平.
- 用于体外细胞培养,高通量RNA测序,生物信息分析,分子对接,位点定向突变和微观温度测试.
- 使用乳酸氧化酶 (LOx) 过度表达的lentivirus来降低乳酸水平.
主要成果:
- 乳酸水平在退化的椎间盘中显著升高.
- 降低乳酸水平缓解了IVDD的进展.
- 高乳酸度诱导了NPC衰老和氧化应激在体外.
- 乳酸通过与Lys39和Leu52在Akt的PH域中的残留物结合,与Akt激酶活性相互作用.
- 乳酸调节下游路径,包括Akt/p21/p27/cyclin D1和Akt/Nrf2/HO-1.
结论:
- 乳酸积累是IVDD发病的一个关键因素.
- 乳酸直接诱导NPC衰老和氧化应激.
- PI3K/Akt信号通路在乳酸诱导的NPC损伤中具有关键作用.
- 乳酸是治疗IVDD的一个有前途的新型治疗点.
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