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肌生成分化中的镁稳态——关注 TRPM7、MagT1 和 SLC41A1 转运蛋白的调节。

Magnesium Homeostasis in Myogenic Differentiation-A Focus on the Regulation of TRPM7, MagT1 and SLC41A1 Transporters.

机构信息

Department of Biomedical and Clinical Sciences Luigi Sacco, Università di Milano, 20157 Milano, Italy.

Pediatric Department, "Vittore Buzzi" Children's Hospital, 20154 Milano, Italy.

出版信息

Int J Mol Sci. 2022 Jan 31;23(3):1658. doi: 10.3390/ijms23031658.

Abstract

Magnesium (Mg) is essential for skeletal muscle health, but little is known about the modulation of Mg and its transporters in myogenic differentiation. Here, we show in C2C12 murine myoblasts that Mg concentration fluctuates during their differentiation to myotubes, declining early in the process and reverting to basal levels once the cells are differentiated. The level of the Mg transporter MagT1 decreases at early time points and is restored at the end of the process, suggesting a possible role in the regulation of intracellular Mg concentration. In contrast, TRPM7 is rapidly downregulated and remains undetectable in myotubes. The reduced amounts of TRPM7 and MagT1 are due to autophagy, one of the proteolytic systems activated during myogenesis and essential for the membrane fusion process. Moreover, we investigated the levels of SLC41A1, which increase once cells are differentiated, mainly through transcriptional regulation. In conclusion, myogenesis is associated with alterations of Mg homeostasis finely tuned through the modulation of MagT1, TRPM7 and SLC41A1.

摘要

镁(Mg)对骨骼肌健康至关重要,但人们对其在成肌分化中的调节及其转运体知之甚少。在这里,我们在 C2C12 鼠成肌细胞中表明,Mg 浓度在其分化为肌管的过程中波动,在该过程早期下降,一旦细胞分化,恢复到基础水平。Mg 转运体 MagT1 的水平在早期时间点下降,并在过程结束时恢复,表明其可能在调节细胞内 Mg 浓度中发挥作用。相比之下,TRPM7 在肌管中迅速下调并不可检测。TRPM7 和 MagT1 的减少是由于自噬引起的,自噬是成肌过程中激活的蛋白水解系统之一,对于膜融合过程至关重要。此外,我们研究了 SLC41A1 的水平,其在细胞分化后增加,主要通过转录调节。总之,成肌发生与 Mg 动态平衡的改变有关,这种改变通过 MagT1、TRPM7 和 SLC41A1 的调节来精细调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e29/8836031/a34d1059e10f/ijms-23-01658-g001.jpg

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