Jie Yin1,2,3,4, Yuying Li1,2,3,4, Hui Han1,2,3,4, Jie Zheng5, Lijian Wang1,2,3,4, Wenkai Ren1,2,3,4, Shuai Chen1,2,3,4, Fei Wu1,2,3,4, Rejun Fang5,6, Xingguo Huang5,7,6, Chunyong Li1,2,3, Bie Tan1,2,3, Xia Xiong1,2,3, Yuzhe Zhang1,2,3, Gang Liu1,2,3, Jiming Yao5,7, Tiejun Li1,2,3,7,6,8, Yulong Yin1,2,3,7,8. 1. Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, P. R. China. 2. Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, Hunan, P. R. China. 3. Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Changsha, Hunan, P. R. China. 4. University of Chinese Academy of Sciences, Beijing, P. R. China. 5. College of Animal Science and Technology, Hunan Agriculture University, Hunan, P. R. China. 6. Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan, P. R. China. 7. Guangdong Wangda Group Academician Workstation for Clean Feed Technology Research and Development in Swine, Guangdong Wangda Group Co., Ltd., GuangDong, P. R. China. 8. National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan, P. R. China.
Abstract
SCOPE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
SCOPE: 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. METHODS AND RESULTS: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. CONCLUSIONS: 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.