低剂量MLN4924通过向SOCS3信号来提高SH-SY5Y细胞活力和迁移
Zelin Lai1, Simin Yang2, Xia Liu2
1Neurosurgery Center, National Key Clinical Specialty, Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Zhujiang Hospital Institute for Brain Science and Intelligence, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, China. laizelin@smu.edu.cn.
Doklady. Biochemistry and biophysics
|January 12, 2026
概括
低剂量MLN4924 (pevonedistat) 通过增加SOCS3表达来提高SH-SY5Y细胞生存和迁移,独立于JAK2/STAT3信号传递. 这一发现澄清了它在神经元细胞中的复杂作用.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- MLN4924 (pevonedistat) 抑制了NEDD8激活酶,通过缩途径影响瘤生长.
- 低剂量MLN4924在癌细胞和神经元中显示出促生存的效果,但其对SH-SY5Y细胞的影响尚不清楚.
研究的目的:
- 研究低剂量MLN4924对SH-SY5Y细胞活力,迁移和神经元外生的影响.
- 阐明潜在的分子机制,包括SOCS3,JAK2和STAT3信号传输的作用.
主要方法:
- 使用CCK-8和Transwell试验评估的细胞活力和迁移.
- 在用增强的绿色光蛋白质等离子体感染的细胞中观察到神经元外生长.
- 蛋白质表达和酸化被Western blot分析;用于探索药物向相互作用的分子对接.
主要成果:
- 0.1μM MLN4924显著增加了SH-SY5Y细胞活力和迁移.
- MLN4924治疗导致神经元外生减少.
- SOCS3表达显著上调,而JAK2和STAT3酸化保持不变.
- 分子对接确定了SOCS3的Glu63作为MLN4924的关键结合残留物.
结论:
- 低剂量MLN4924通过SOCS3向增强SH-SY5Y细胞活力和迁移.
- 观察到的效应独立于JAK2/STAT3信号通路.
- MLN4924对神经元细胞表现出复杂的,剂量依赖的作用,影响生存和形态.
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