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氨酸乳酸化调节ATF4介导的应激反应在葡萄糖饥饿下在狗血类肉瘤中

Tamami Suzuki¹, Kazuki Heishima^2,3,4, Jumpei Yamazaki^5,6

¹Laboratory of Comparative Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Frontiers in veterinary science

|March 2, 2026

概括

在葡萄糖稀缺期间,基因乳酸化转移到基因起始部位,调节犬血类肉瘤细胞中的压力反应和免疫相互作用,以促进瘤存活.

科学领域:

生物化学生物化学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

瘤细胞中的有氧糖解会产生多余的乳酸盐,通过基因激素乳化影响基因表达.
在葡萄糖受限条件下,基斯乳酸的作用尚不清楚.

研究的目的:

为了研究胰岛素乳酸酶在犬血肉瘤 (HSA) 细胞中葡萄糖剥夺期间的功能.
了解 lysine 乳糖化如何影响基因表达和在营养压力下的细胞行为.

主要方法:

在HSA细胞中进行葡萄糖剥夺实验.
使用质谱学分析基因素乳化模式.
RNA测序以评估基因表达变化.
[U-¹³C]氨酸追踪研究代谢途径.
在ATF4多克隆淘汰实验中.
对HSA患者组织的免疫组织化学分析.

主要成果:

缺乏葡萄糖降低了全球基因素乳化,但在转录起始点 (TSS) 丰富了乳化.
在TSS的乳化向了参与应激反应,阿斯巴拉金合成和免疫调节的基因,包括ATF4向.
压力反应基因表达增加,依赖ATF4.
在葡萄糖稀缺的情况下,HSA细胞从谷氨酸中合成阿斯巴拉金.
在患者组织中观察到异质的H3K18la水平,低乳化与M2样巨细胞透相关.

结论:

在葡萄糖剥夺期间,氨酸乳酸化动态地重新分配到TSS,改变基因转录.
这一过程支持瘤细胞的生存,并在营养压力下调节瘤微环境.
基斯乳化在瘤适应新陈代谢挑战方面发挥着至关重要的作用.

关键词:

狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗葡萄糖葡萄糖葡萄糖是一种血性肉瘤 (hemangiosarcoma) 是一个基因素乳酸化基因素乳酸化压力反应应对压力的反应.瘤代谢瘤代谢

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