Increased O-GlcNAcylation induces myocardial hypertrophy
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Increased O-GlcNAcylation induces myocardial hypertrophy Xiaoli Chen 1 & Li Zhang 1 & Hui He 2 & Yikai Sun 3 & Qin Shen 3 & Linsheng Shi 1 Received: 31 July 2020 / Accepted: 31 August 2020 / Editor: Tetsuji Okamoto # The Society for In Vitro Biology 2020
Abstract Myocardial hypertrophy is a common precursor of many diseases, and it can lead to myocardial ischemia and weaken cardiac contractility. High-sugar diets and diabetes are high risk factors for cardiac hypertrophy. O-GlcNAcylation, a dynamic and ubiquitous post-translational glycosylation of proteins on serine/threonine residues, has been usually considered as a nutrient sensor. Hyperglycemia, hyperlipidemia, and hyperinsulinemia lead to an enhancement of protein O-GlcNAcylation; however, whether excessive O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of proteins in cardiomyocytes causes cardiac hypertrophy remains unclear. In this study, we treated cultured primary cardiomyocytes or mice with streptozotocin (STZ) or PUGNAc, two inhibitors of O-GlcNAcase (OGA) to elevate cellular O-GlcNAcylation. We found that increased OGlcNAcylation induced hypertrophy-like changes by detecting cardiomyocyte morphology or measuring the thickness of mice left ventricular wall with HE staining. The mRNA levels of cardiac hypertrophy–related genes, atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC), are increased in drug treatment groups. We further found that the increase of OGlcNAcylation upregulated the activity of cAMP response element-binding protein (CREB) in cultured primary cells and in vivo by detecting the phosphorylation level of CREB by Western blot and the mRNA levels of CREB downstream targets C-fos and C-jun by RT-qPCR. These results suggest that the increased O-GlcNAcylation in cardiomyocytes is associated with cardiac hypertrophy both in cultured cells and in vivo, which provides possible intervention targets and approaches for the clinical treatment of myocardial hypertrophy triggered by high carbohydrate diets. Keywords O-GlcNAcylation . Myocardial hypertrophy . Streptozotocin . PUGNAc . CREB
Introduction Myocardial hypertrophy, a thickening of the heart muscle in response to the overload of hemodynamic pressures, is a common precursor of many cardiovascular diseases (Schirone et al. 2017). Myocardial hypertrophy can induce myocardial ischemia and weaken cardiac contractility, which eventually leads to cardiovascular diseases (van der Velden et al. 2018). Thus, it is important to study the pathogenesis and etiology of cardiac hypertrophy to prevent and treat cardiovascular diseases. Xiaoli Chen and Li Zhang contributed equally to this work. * Linsheng Shi [email protected] 1
Department of Cardiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
2
Department of Human Anatomy, Medical School of Nantong University, Nantong, Jiangsu, China
3
Department of Biochemistry, Medical School of Nantong University, Nantong, Jiangsu, China
Many factors may increase the risk of cardiac hypertrop
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