Site-specific N -glycoproteme Analysis Reveals Up-regulated Sialylation and Core Fucosylation during Transient Regeneration Loss in Neonatal Mouse Hearts

Myocardial infarction (MI) is one of the leading causes of deaths worldwide. Due to the incapability of regeneration, the cardiomyocytes loss with MI is replaced by fibrotic scar tissue, which eventually leads to heart failure. Reconstructing regeneration of the adult human heart has been recognized...

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Published in:Journal of proteome research 2020-05
Main Authors: Li, Jun, Jia, Li, Hao, Zhifang, Xu, Yintai, Shen, Jiechen, Ma, Chen, Wu, Jingyu, Zhao, Ting, Zhi, Yuan, Li, Pengfei, Li, Jing, Zhu, Bojing, Sun, Shisheng
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Language:English
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Summary:Myocardial infarction (MI) is one of the leading causes of deaths worldwide. Due to the incapability of regeneration, the cardiomyocytes loss with MI is replaced by fibrotic scar tissue, which eventually leads to heart failure. Reconstructing regeneration of the adult human heart has been recognized as a promising strategy for cardiac therapeutics. The neonatal mouse heart, which possesses transient regenerative capacity at the first week after birth, represents an ideal model to investigate processes associated with cardiac regeneration. In this work, an integrated glycoproteomic and proteomic analysis was performed to investigate the differences in glycoprotein abundances and site-specific glycosylation between post-neonatal day 1 (P1) and day 7 (P7) of mouse hearts. By large-scale profiling and quantifying more than 2,900 intact -glycopeptides in neonatal mouse hearts, we identified 227 altered -glycopeptides between P1 and P7 hearts. By extracting protein changes from global proteome data, the normalized glycosylation changes for site-specific glycans were obtained, which showed heterogeneity on glycosites and glycoproteins. Systematic analysis of the glycosylation changes demonstrated an overall up-regulation of sialylation and core fucosylation in P7 mice. Notably, the up-regulated sialylation was a comprehensive result of increased sialylated glycans with Neu5Gc, with both Neu5Gc and core fucose, and decreased sialylated glycans with Neu5Ac. The up-regulated core fucosylation was resulted from the increase of glycans containing both core fucose and Neu5Gc, but not glycans containing sole core fucose. The data provide a valuable resource for future functional and mechanism studies on heart regeneration and discovery of novel therapeutic targets. All mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD017139.
ISSN:1535-3907