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在限制谷氨胺时,AMPK在TET2下调的白血病细胞中的激活

Ahsen Merve Bayrak^1,2, Burcu Yucel^2,3,4

¹Istanbul Medeniyet University Institute of Graduate Studies, Department of Molecular Medicine, Istanbul, Türkiye.

Medeniyet medical journal

|October 1, 2024

概括

经TET2阻断的急性髓性白血病细胞对谷氨酸缺乏的抵抗性增加. 这种耐药性与高胺合成酶和P-AMPKα水平有关,这表明它在癌症细胞存活中起作用.

科学领域:

癌症生物学癌症生物学
代谢重编程代谢重编程
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

代谢重新连接是癌症的标志,细胞经常表现出增加的营养需求.
虽然细胞可以合成谷氨胺,但一些癌症依赖外部来源生存和增殖.
TET2是一种参与DNA脱甲基化的瘤抑制基因,在急性髓性白血病 (AML) 等癌症中经常发生突变.

研究的目的:

研究HL-60AML细胞中TET2下调和谷氨胺代谢之间的关系.
在不同的谷氨酸条件下,评估TET2敲击对细胞增殖的影响.
分析关键代谢酶和信号蛋白的表达,以响应TET2调节和谷氨酸可用性.

主要方法:

在HL-60细胞中使用短毛RNA (shRNA) 技术降低了TET2的调节.
细胞增殖测定在正常和缺乏谷氨胺的介质中进行.
谷氨酸合成酶 (GLUL) 的mRNA和蛋白质水平分别使用RT-qPCR和免疫阻塞量化.
还评估了-AMPKα (P-AMPKα) 蛋白质水平.

主要成果:

与对照细胞相比,在低氨酸基质介质中,TET2-knockdown HL-60细胞的数量减少,但活力增加.
在缺乏谷氨酸的条件下,在TET2敲击细胞中,谷氨酸合成酶mRNA表达显著上调.
在低谷氨胺介质中培养的TET2敲击细胞中,酸-AMPKα蛋白水平升高.

结论:

TET2敲击下来的HL-60细胞表现出对谷氨酸缺乏的增强抵抗力.
在低谷氨酸条件下对谷氨酸合成酶的升级可能会导致这些细胞中观察到的谷氨酸成.
P-AMPKα的增加表明这种信号通路在TET2敲击后调解细胞适应谷氨酸缺乏的过程中可能发挥作用.

关键词:

在AML,AML就是AML.这就是AMPKK.谷氨胺的代谢过程这就是TET2表达式.通过shRNA介导的基因沉默.

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