TIM-3/Gal-9相互作用会影响急性髓性白血病细胞系中的葡萄糖和脂质代谢
Mahnaz Rezaei1, Mustafa Ghanadian2, Behrooz Ghezelbash1
1Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Frontiers in immunology
|November 29, 2023
概括
在T细胞免疫球蛋白和粘素域-3 (TIM-3) 和加勒-9 (Gal-9) 的相互作用促进葡萄糖和脂质代谢在急性髓性白血病 (AML) 细胞. 这种相互作用增强了白血病细胞的生存和增殖.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 代谢研究研究 代谢研究
背景情况:
- T细胞免疫球蛋白和粘素域-3 (TIM-3) 是一种免疫调节剂,也存在于急性髓性白血病 (AML) 细胞上.
- 蒂姆-3在白血病细胞的存活和增殖中发挥作用.
研究的目的:
- 研究TIM-3与其连接物加勒-9 (Gal-9) 相互作用对AML细胞系中的葡萄糖和脂质代谢的影响.
- 了解这种相互作用如何影响白血病细胞行为.
主要方法:
- 使用了HL-60和THP-1的AML细胞系.
- 通过流式细胞计量评估TIM-3表达.
- 使用实时PCR检查了关键代谢基因 (GLUT-1, HK-2, PFKFB-3, G6PD, ACC-1, ATGL, CPT-1A) 的mRNA表达.
- 测量了葡萄糖,乳酸,GSH,G6PD活性以及自由脂肪酸 (FFAs).
- 使用MTT试验确定细胞增殖.
主要成果:
- 在AML细胞中,Gal-9显著上调GLUT-1,HK-2,PFKFB-3,ACC-1,CPT-1A和G6PD的mRNA表达和G6PD活动.
- 在Gal-9的存在下观察到细胞外FFAs,葡萄糖消耗,乳酸释放,细胞GSH和细胞增殖的增加.
- 这些代谢变化以时间依赖的方式发生.
结论:
- TIM-3/Gal-9结合诱导有氧糖解并改变AML细胞中的脂质代谢.
- 这种相互作用提供了对氧化应激的保护,有利于白血病细胞的存活和增殖.
- 这些发现突出了支持AML进展的关键代谢途径.
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