Little involvement of recycled-amino acids from proteasomal proteolysis in de novo protein synthesis

Little involvement of recycled-amino acids from proteasomal proteolysis in de novo protein synthesis
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DOI:
10.1016/j.bbrc.2022.09.113
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发表时间:
2022-10-10
影响因子:
3.1
通讯作者:
Nagatomi,Ryoichi
Nagatomi,Ryoichi
中科院分区:
生物学4区
文献类型:
--
作者:
Osana,Shion;Kitajima,Yasuo;Nagatomi,Ryoichi

文献摘要

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成肌细胞的完整性对骨骼肌再生至关重要。许多细胞内蛋白质被蛋白酶体降解,并通过蛋白质降解途径被氨肽酶转化为氨基酸。虽然我们以前报道过它对成肌细胞完整性的重要性,但其相关机制仍不清楚。本研究以蛋白质水解产物的可重复利用性为研究对象,旨在阐明蛋白酶体和氨肽酶介导的蛋白质合成调控机制。蛋白酶体抑制降低蛋白质合成,但蛋白酶体蛋白水解产生的氨基酸不能再用于C2C12成肌细胞的新蛋白合成。另一方面,蛋白酶体和氨肽酶抑制降低C2C12成肌细胞内ATP水平。因此,这表明由这些蛋白水解系统产生的氨基酸可以通过其代谢而不是福尔德新蛋白合成再用于ATP生产。这些发现表明,蛋白酶体和氨肽酶被认为是参与蛋白质合成,通过细胞内的能量产生的氨基酸代谢,从而维持成肌细胞的完整性。
Myoblast integrity is essential for skeletal muscle regeneration. Many intracellular proteins are degraded by the proteasome and converted to amino acids by aminopeptidases through the protein degradation pathway. Although we previously reported its importance for myoblast integrity, the involved mechanism remains unclear. In this study, we focused on the reusability of proteolytic products to elucidate the regulatory mechanism of protein synthesis mediated by the proteasome and aminopeptidases. Proteasome inhibition decreased protein synthesis, but recycled-amino acids derived from proteasomal proteolysis were not reused forde novoprotein synthesis in C2C12 myoblasts. On the other hand, proteasome and aminopeptidase inhibition decreased intracellular ATP levels in C2C12 myoblasts. Therefore, it was indicated that amino acids produced by these proteolytic systems may be reutilized for ATP production through its metabolism, not forde novoprotein synthesis. These findings suggested the proteasome and aminopeptidases are thought to be involved in protein synthesis through intracellular energy production by recycled-amino acid metabolism, thereby maintaining myoblast integrity.