| Literature DB >> 30779965 |
Phil Jun Kang1, Jie Zheng2, Gilju Lee3, Daryeon Son4, In Yong Kim5, Gwonhwa Song6, Gyuman Park7, Seungkwon You8.
Abstract
Reprogramming of 'adult' differentiated somatic cells to 'embryonic' pluripotent stem cells accompanied by increased rate of glycolysis. Conversely, glycolysis triggers accumulation of advanced glycation end products (AGEs), a potential causative factor in aging, by promoting methylglyoxal production. Therefore, it is reasonable that pluripotent stem cells (PSCs) would specifically regulate glycolysis to maintain their embryonic features. In this study, we focused on glycine decarboxylase (GLDC), a key enzyme in the glycine cleavage system that regulates glycolysis and methylglyoxal production in cancer. GLDC was exclusively expressed in PSCs, and inhibition of this enzyme induced alterations of metabolome and AGE accumulation, thereby suppressing the embryonic pluripotent state. Surprisingly, the level of accumulated AGEs in somatic cells gradually decreased during reprogramming, ultimately disappearing in iPSCs. In addition, ectopic expression of GLDC or treatment with the AGE inhibitor LR-90 promoted reprogramming. Together, these findings suggest that GLDC-mediated regulation of glycolysis and controlling AGE accumulation is related to maintenance and induction of pluripotency.Entities:
Keywords: Advanced glycation end product (AGE); Glycine decarboxylase (GLDC); Glycolysis; Methylglyoxal; Pluripotent stem cell; Reprogramming
Mesh：
Substances：
Year: 2019 PMID： 30779965 DOI： 10.1016/j.ymben.2019.02.003
Source DB: PubMed Journal: Metab Eng ISSN： 1096-7176 Impact factor: 9.783