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多重转录分析揭示了2-脱氧-d-葡萄糖对基因表达的影响,与原始人类单细胞和单细胞衍生的巨细胞中展开的蛋白质反应和集成的应激反应有关

Y S Tamayo-Molina¹, Paula A Velilla¹, Lady Johana Hernández-Sarmiento¹

¹Immunovirology Group, Faculty of Medicine, University of Antioquia, Calle 70 No. 52-21, Medellin, Colombia.

Biochimica et biophysica acta. General subjects

|June 8, 2023

概括

糖溶性抑制剂2-脱氧-d-葡萄糖 (2-DG) 诱导了内质网膜 (ER) 的压力,并改变了人类单细胞和巨细胞中的基因表达. 这项研究确定了参与综合应激反应的特定基因,这表明它在恢复蛋白质平衡中发挥了作用.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
代谢途径代谢途径

背景情况:

2-脱氧-d-葡萄糖 (2-DG) 通过向六酶和糖异构酶来抑制糖解.
众所周知,2-DG会诱导内质网膜 (ER) 应激,激活未折叠的蛋白质反应.
人类初级细胞中由2-DG调节的特定的ER压力相关基因在很大程度上仍然没有表征.

研究的目的:

为了研究2DG治疗后单细胞和单细胞衍生巨细胞 (MDMs) 的转录变化.
为了确定由2-DG诱导的ER压力特异性基因表达特征在人类原发性免疫细胞中.
阐明2-DG在调节细胞应激反应中的作用.

主要方法:

来自2-DG治疗细胞的RNA测序数据集的生物信息学分析.
在对照和2-DG治疗单细胞和MDM之间识别差异表达基因 (DEGs).
使用定量逆转录PCR (RT-qPCR) 验证关键基因表达变化.

主要成果:

在2-DG治疗的单细胞和MDM中,共发现了95种常见的DEG,其中74种是上调调的,21种是下调调的.
不同表达的基因与综合应激反应途径有显著的关联.
参与赫索胺生物合成途径和曼诺代谢的关键基因也被2-DG治疗调节.

结论:

2-DG治疗诱导了人类初级单细胞和巨细胞中的特定基因表达程序.
观察到的基因表达特征表明,2-DG触发了旨在恢复蛋白质平衡的机制.
2-DG作为一种压力诱导剂,显著改变单细胞和巨细胞的代谢和压力状态.

关键词:

2 - 脱氧 - d - 葡萄糖的二氧化碳.细胞内膜网膜应激压力人类初级细胞是人类的初级细胞.综合应激反应综合应激反应蛋白质的糖化化是蛋白质的糖化.不折叠的蛋白质反应反应

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