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- Title
O-GlcNAc Transferase is a Pro-Survival Enzyme in Post-Hypoxic Cardiac Myocytes.
- Authors
Ngoh, Gladys Afor; Watson, Lewis J.; Jones, Steven P.
- Abstract
The post-translational modification, O-linked β-N-acetylglucosamine (O-GlcNAc), is a metabolic and nutrient sensor which exerts cardioprotective effects. However, a paucity of information exists regarding the direct regulation of O-GlcNAc levels in the heart. We evaluated the role of O-GlcNAc transferase (OGT, which adds OGlcNAc to proteins) on cardiac myocyte survival following hypoxiareoxygentaion. We infected isolated cardiac myocytes (n=4-5/group) with adenovirus carrying the OGT gene (AdOGT), or treated with an OGT inhibitor (TT04), and subjected them to hypoxia and reoxygenation. Whole cell lysates were immunoblotted for O-GlcNAc levels and myocyte damage following reoxygenation was spectrophotometrically assessed via LDH release. Timelapse fluorescence microscopy using tetramethylrhodamine methyl ester (TMRM) was used to assess the post-hypoxic loss of mitochondrial membrane potential. AdOGT significantly augmented O-GlcNAc levels (p<0.05 compared to control), produced a significant reduction in LDH release, and preserved mitochondrial membrane potential. OGT inhibition (TT04) significantly reduced (p<0.05) O-GlcNAc levels, exacerbated LDH release, and hastened the loss of mitochondrial membrane potential. We conclude that OGT is a previously unrecognized, pro-survival enzyme in cardiac myocytes that exerts its effects via augmentation of O-GlcNAc levels.
- Subjects
ENZYMES; GLUCOSAMINE; TRANSFERASES; MYOCARDIUM; MUSCLE cells; HYPOXEMIA; FLUORESCENCE microscopy; MITOCHONDRIAL membranes
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA800
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a800