Department of Cooperative Medical Research, Head Office for Regional Collaboration and Innovation, Shimane University, 89-1 Enya-Cho, Izumo, Shimane, 693-8501, Japan.
Mol Biol Rep. 2024 Oct 15;51(1):1053. doi: 10.1007/s11033-024-10009-6.
Monoclonal nonspecific suppressor factor β (MNSFβ), a ubiquitously expressed member of the ubiquitin-like protein family, is associated with diverse cell regulatory functions. It has been implicated in glycolysis regulation and cell proliferation enhancement in the macrophage-like cell line Raw264.7. This study aims to show that HIF-1α regulates MNSFβ-mediated metabolic reprogramming.
In Raw264.7 cells, MNSFβ siRNA increased the oxygen consumption rate and reactive oxygen species (ROS) production but decreased ATP levels. Cells with MNSFβ knockdown showed a markedly increased ATP reduction rate upon the addition of oligomycin, a mitochondrial ATP synthase inhibitor. In addition, MNSFβ siRNA decreased the expression levels of mRNA and protein of HIF-1α-a regulator of glucose metabolism. Evaluation of the effect of MNSFβ on glucose metabolism in murine peritoneal macrophages revealed no changes in lactate production, glucose consumption, or ROS production.
MNSFβ affects both glycolysis and mitochondrial metabolism, suggesting HIF-1α involvement in the MNSFβ-regulated glucose metabolism in Raw264.7 cells.
单克隆非特异性抑制因子β（MNSFβ）是泛素样蛋白家族中的一个成员，与多种细胞调节功能有关。它已被牵连到巨噬细胞样细胞系 Raw264.7 中的糖酵解调节和细胞增殖增强。本研究旨在表明 HIF-1α 调节 MNSFβ 介导的代谢重编程。
在 Raw264.7 细胞中，MNSFβ siRNA 增加了耗氧量和活性氧（ROS）的产生，但降低了 ATP 水平。用线粒体 ATP 合酶抑制剂寡霉素处理时，MNSFβ 敲低的细胞表现出明显增加的 ATP 还原率。此外，MNSFβ siRNA 降低了葡萄糖代谢调节剂 HIF-1α 的 mRNA 和蛋白表达水平。在小鼠腹腔巨噬细胞中评估 MNSFβ 对葡萄糖代谢的影响，发现乳酸生成、葡萄糖消耗或 ROS 产生没有变化。
MNSFβ 影响糖酵解和线粒体代谢，表明 HIF-1α 参与了 Raw264.7 细胞中 MNSFβ 调节的葡萄糖代谢。
