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O‐GlcNAc Signaling Regulates Cardiomyogenesis of Cardiac Progenitor Cells
Author(s) -
Zafir Ayesha,
Hamid Tariq,
Hill Bradford,
Powell David,
Li Qianhong,
Bolli Roberto,
Jones Steven P
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.826.2
Background Cardiac progenitor cells (CPCs) possess inherent, though poorly understood, reparative capabilities that may be important in the setting of myocardial infarction. We investigated the role of the cardioprotective stress signal O‐GlcNAc in cardiomyogenic differentiation of CPCs. Methods/Results CPCs (c‐kit + /lin − ) were pretreated overnight (~16 h) with an OGA inhibitor Thiamet‐G (Th‐G; 0.001mM) or with DON (0.025mM), an inhibitor of the rate‐limiting enzyme of the hexosamine biosynthetic pathway GFAT. CPCs were cultured for 5 days while stimulating differentiation with 10 nM dexamethasone. Proteomic analyses indicated differentiation reduced GFAT2 expression. Th‐G augmented O‐GlcNAc levels and attenuated cardiomyogenic differentiation of CPCs, evidenced by significantly reduced expression (according to qPCR) of the cardiac‐specific transcription factor Nkx2.5. Conversely, reduction of O‐GlcNAc levels (via DON) potentiated Nkx2.5 expression. Conclusions Augmenting the O‐GlcNAc stress signal antagonizes cardiomyogenic differentiation of CPCs. Our findings indicate a new mechanism regulating cardiomyogenic differentiation of CPCs. Future studies will determine whether such an effect is pro‐ or maladaptive in the heart following infarction. Financial support: NIH, AHA.