| First Author | Matsuno M | Year | 2023 |
| Journal | Front Endocrinol (Lausanne) | Volume | 14 |
| Pages | 1122125 | PubMed ID | 37033243 |
| Mgi Jnum | J:345405 | Mgi Id | MGI:7462824 |
| Doi | 10.3389/fendo.2023.1122125 | Citation | Matsuno M, et al. (2023) O-GlcNAcylation-induced GSK-3beta activation deteriorates pressure overload-induced heart failure via lack of compensatory cardiac hypertrophy in mice. Front Endocrinol (Lausanne) 14:1122125 |
| abstractText | O-GlcNAc transferase (OGT) modulates many functions of proteins via O-GlcNAcylation that adds O-linked beta-N-acetylglucosamine (O-GlcNAc) to the serine/threonine residues of proteins. However, the role of O-GlcNAcylation in cardiac remodeling and function is not fully understood. To examine the effect of O-GlcNAcylation on pressure overload-induced cardiac hypertrophy and subsequent heart failure, transverse aortic constriction (TAC) surgery was performed in wild type (WT) and Ogt transgenic (Ogt-Tg) mice. Four weeks after TAC (TAC4W), the heart function of Ogt-Tg mice was significantly lower than that of WT mice (reduced fractional shortening and increased ANP levels). The myocardium of left ventricle (LV) in Ogt-Tg mice became much thinner than that in WT mice. Moreover, compared to the heart tissues of WT mice, O-GlcNAcylation of GSK-3beta at Ser9 was increased and phosphorylation of GSK-3beta at Ser9 was reduced in the heart tissues of Ogt-Tg mice, resulting in its activation and subsequent inactivation of nuclear factor of activated T cell (NFAT) activity. Finally, the thinned LV wall and reduced cardiac function induced by TAC4W in Ogt-Tg mice was reversed by the treatment of a GSK-3beta inhibitor, TDZD-8. These results imply that augmented O-GlcNAcylation exacerbates pressure overload-induced heart failure due to a lack of compensatory cardiac hypertrophy via O-GlcNAcylation of GSK-3beta, which deprives the phosphorylation site of GSK-3beta to constantly inactivate NFAT activity to prevent cardiac hypertrophy. Our findings may provide a new therapeutic strategy for cardiac hypertrophy and subsequent heart failure. |
