Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, Hunan, P. R. China.
Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201600754. Epub 2017 Jul 20.
Lysine (Lys) is a common limiting amino acids (AA) for humans and animals and plays an important role in cell proliferation and metabolism, while metabolism of Lys deficiency and its dipeptide is still obscure. Thus, this study mainly investigated the effects of Lys deficiency and Lys-Lys dipeptide on apoptosis and AA metabolism in vitro and in vivo models.
Lys deficiency induced cell-cycle arrest and apoptosis and upregulated Lys transporters in vitro and in vivo. SLC7A11, a cystine-glutamate antiporter, was markedly upregulated by Lys deficiency and then further mediated cystine uptake and glutamate release, which was negatively regulated by cystine and glutamate transporters. Meanwhile, Lys deprivation upregulated pept1 expression, which might improve Lys-Lys dipeptide absorption to compensate for the reduced Lys availability. Lys-Lys dipeptide alleviated Lys deficiency induced cell-cycle arrest and apoptosis and influenced AA metabolism. Furthermore, the mammalian target of rapamycin signal might be involved in sensing cellular Lys starvation and Lys-Lys dipeptide.
Altogether, these studies suggest that Lys deficiency impairs AA metabolism and causes apoptosis. Lys-Lys dipeptide serves as a Lys source and alleviates Lys deficiency induced cellular imbalance.
赖氨酸（Lys）是人和动物常见的限制氨基酸（AA），在细胞增殖和代谢中发挥重要作用，而 Lys 缺乏及其二肽的代谢仍不清楚。因此，本研究主要研究了 Lys 缺乏和 Lys-Lys 二肽对体外和体内模型中细胞凋亡和 AA 代谢的影响。
Lys 缺乏在体外和体内诱导细胞周期停滞和细胞凋亡，并上调 Lys 转运体。胱氨酸-谷氨酸反向转运体 SLC7A11 被 Lys 缺乏显著上调，然后进一步介导胱氨酸摄取和谷氨酸释放，胱氨酸和谷氨酸转运体对其进行负调控。同时，Lys 剥夺上调了 pept1 的表达，这可能改善 Lys-Lys 二肽的吸收，以弥补减少的 Lys 可利用性。Lys-Lys 二肽缓解了 Lys 缺乏诱导的细胞周期停滞和细胞凋亡，并影响 AA 代谢。此外，雷帕霉素靶蛋白信号可能参与感知细胞 Lys 饥饿和 Lys-Lys 二肽。
总之，这些研究表明 Lys 缺乏会损害 AA 代谢并导致细胞凋亡。Lys-Lys 二肽可作为 Lys 的来源，缓解 Lys 缺乏引起的细胞失衡。
