Premium
Nicotinamide adenine dinucleotide hydrate (NAD) contributes to the regulation of O‐linked‐N‐acetylglucosamine (O‐GlcNAc) levels on cardiomyocyte proteins
Author(s) -
Zou Chenhang,
Zou Luyun,
Young Martin E,
Chatham John C
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.1097.3
Subject(s) - nad+ kinase , nicotinamide adenine dinucleotide , chemistry , nicotinamide adenine dinucleotide phosphate , biochemistry , nicotinamide , n acetylglucosamine , hydrate , microbiology and biotechnology , biology , enzyme , organic chemistry , oxidase test
The modification of serine and threonine residues of nucleocytoplasmic proteins by O‐GlcNAc plays a central role in mediating the cellular response to diverse stress stimuli. There is also increasing recognition that NAD mediates cellular stress responses, through modifying protein acetylation and poly‐ADP ribosylation. The goal of this study, therefore, was to determine whether NAD also influences protein O‐GlcNAcylation. Neonatal rat ventricular cardiomyocytes (NRVM) were treated with NAD (0.06mM, 0.125mM, 0.25mM, 0.5mM, and 1mM) for 6h. We found that NAD (≥ 0.25mM) significantly decreased O‐GlcNAc levels by >50%. We also evaluated O‐GlcNAc levels 3, 6, 12 and 24hs after treatment with 0.25mM NAD. We observed a clear time dependent decrease, with a minimum at 6hrs and a partial return to baseline levels at 12hrs. Despite the marked effect of NAD on decreasing NRVM O‐GlcNAc levels, there were no changes in the protein levels of O‐GlcNAc transferase (OGT) or O‐GlcNAcase (OGA), which regulate O‐GlcNAc synthesis and degradation respectively. This suggests that NAD might reduce O‐GlcNAc levels by decreasing rates of O‐GlcNAc synthesis or increasing degradation. These data suggest for the first time that NAD contributes to the regulation of protein O‐GlcNAcylation, and suggests NAD may influence cellular stress‐signaling through this post‐translational modification. NIH HL079364 , HL101192