Peroxiredoxin-2 nitrosylation facilitates cardiomyogenesis of mouse embryonic stem cells via XBP-1s/PI3K pathway

Publication date: August 2016
Source:Free Radical Biology and Medicine, Volume 97
Author(s): Bowen Wu, Hao Yu, Yifan Wang, Zongfu Pan, Yihan Zhang, Tong Li, Lu Li, Weichen Zhang, Lijun Ge, Ying Chen, Choe Kyong Ho, Danyan Zhu, Xin Huang, Yijia Lou
Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S-nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes, Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity, causing transient endogenous hydrogen peroxide (H2O2) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis.

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