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HDACs are O‐GlcNAc modified and OGT O‐GlcNAcylation is decreased with acute exercise
Author(s) -
Medford Heidi M,
Marsh Susan A
Publication year - 2013
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.27.1_supplement.1134.2
Subject(s) - cytosol , serine , rest (music) , chemistry , threonine , cardiac hypertrophy , repressor , muscle hypertrophy , biochemistry , medicine , microbiology and biotechnology , gene , phosphorylation , transcription factor , enzyme , biology
Chronic exercise promotes beneficial morphological and physiological cardiac changes, termed physiological cardiac hypertrophy. Class I HDACs 1–3,8 promote, while class II HDACs 4–7,9,10 inhibit hypertrophy in pressure‐overloaded hearts. HDAC signaling in hypertrophy occurs in complex with transcriptional co‐repressors mSin3A and REST. The post‐translational attachment of O‐GlcNAc by OGT to serine and threonine residues of proteins confers acute cardioprotection, and OGT is known to complex with REST transcriptional co‐repressor mSin3A. We hypothesized that chromatin modifying proteins would be O‐GlcNAcylated and that this would be altered in mouse hearts by acute exercise. 15 or 30 minutes of treadmill running did not elicit changes in cardiac fractions of O‐GlcNAc, OGT, OGA, HDACs 1–5, REST, and mSin3A. Independent of exercise, we found HDACs 2–5 and mSin3A in cytosol as well as nuclear fractions; HDAC2 and mSin3A were predominantly nuclear. Cytosolic protein O‐GlcNAcylation was lower in exercised hearts after 15min but higher in nuclear fractions after 15min and 30min. Immunoprecipitation showed decreased OGT O‐GlcNAcylation and decreased association of OGT with REST in response to exercise, independent of time. HDACs 1,2,4,5 were O‐GlcNAcylated, with no effect of exercise or time. We are first to demonstrate HDAC O‐GlcNAcylation and the OGT/REST interaction. This is a significant finding as it links the putatively pathological REST/mSin3A/HDAC complex to OGT and O‐GlcNAc in exercise‐induced cardiac hypertrophy.