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Acute effects of increased hexosamine biosynthesis and protein O‐GlcNAcylation on cardiac gene expression
Author(s) -
Chatham John C,
Bray Molly S,
Young Martin E
Publication year - 2010
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.24.1_supplement.1036.15
Subject(s) - wnt signaling pathway , glucosamine , gene , gene expression , signal transduction , mapk/erk pathway , microbiology and biotechnology , pi3k/akt/mtor pathway , chemistry , biology , biochemistry
Increased levels of O‐linked N‐acetylglucosamine (O‐GlcNAc) on nucleocytoplasmic proteins have been implicated in attenuating ischemic injury as well as mediating the adverse effects of diabetes on the heart. However, little is known regarding the effects of altered protein O‐GlcNAcylation on cardiomyocyte gene expression. Therefore, the purpose of the present study was to examined the acute (6 hours) effects of increasing protein O‐GlcNAcylation on global gene expression in neonatal rat ventricular cardiomyocyte (NRVMs), by activating the hexosamine biosynthesis pathway (5mM glucosamine), or inhibiting O‐GlcNAcase (100μM PUGNAc). Glucosamine significantly altered the expression of 1650 genes of which 775 were induced and 845 repressed. Gene ontology analysis revealed effects on stress response pathways following glucosamine treatment. KEGG pathway analyses indicated that MAPK signaling and cell cycle pathways were significantly modified by glucosamine (p<0.05) there was also a trend towards modulation of PPAR and mTOR pathways. PUGNAc significantly altered 653 genes of which 253 were induced and 400 repressed; pathway analysis indicated that these genes were associated with p53 and Wnt signaling pathways. These data suggest that alterations in O‐GlcNAc turnover contribute to regulation of cardiac gene expression. Grants: USDA/ARS 6250‐51000‐044 (MEY) & NIH HL067464/HL079364 (JCC).