Peroxiredoxin-2 nitrosylation facilitates cardiomyogenesis of mouse embryonic stem cells via XBP-1s/PI3K pathway.
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.
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Science and Technology Innovation Team for Stem Cell Translational Medicine of Cardiovascular Disease of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Bowen
B
Wu
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Chu Kochen Honors College, Zhejiang University, Hangzhou 310058, China.
Hao
H
Yu
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Chu Kochen Honors College, Zhejiang University, Hangzhou 310058, China.
Yifan
Y
Wang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Zongfu
Z
Pan
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Yihan
Y
Zhang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Tong
T
Li
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Science and Technology Innovation Team for Stem Cell Translational Medicine of Cardiovascular Disease of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Lu
L
Li
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Chu Kochen Honors College, Zhejiang University, Hangzhou 310058, China.
Weichen
W
Zhang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Lijun
L
Ge
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Chu Kochen Honors College, Zhejiang University, Hangzhou 310058, China.
Ying
Y
Chen
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; College of International Education, Zhejiang University, Hangzhou 310058, China; Haeju Medical University, Haeju, Democratic People's Republic of Korea.
Choe Kyong
CK
Ho
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Science and Technology Innovation Team for Stem Cell Translational Medicine of Cardiovascular Disease of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Danyan
D
Zhu
Key Science and Technology Innovation Team for Stem Cell Translational Medicine of Cardiovascular Disease of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Cardiovascular Key Laboratory of Zhejiang Province, The 2nd Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: xh@zju.edu.cn.
Xin
X
Huang
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Science and Technology Innovation Team for Stem Cell Translational Medicine of Cardiovascular Disease of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: yijialou@zju.edu.cn.
Yijia
Y
Lou
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D040901:Proteomics; D026422:S-Nitrosoglutathione / Q000378:metabolism; D015398:Signal Transduction; D000071717:X-Box Binding Protein 1 / Q000235:genetics*
D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D019869:Phosphatidylinositol 3-Kinases
Cardiomyogenesis; Embryonic stem cells; Hydrogen peroxide; Nitrosylation; Peroxiredoxin-2; S-nitrosoglutathione; X-box binding protein