Decreasing O-GlcNAcylation of 8-oxoguanosine DNA Glycosylase (OGG1) in Cardiac Myocytes Cultured in High Glucose Leads to Improvement of DNA Repair and Mitochondrial Function

DNA damage in cardiac myocytes resulting from increased oxidative stress is an important factor in the pathogenesis of diabetic cardiomyopathy. Although DNA repair machinery has been described in the cardiac myocyte, the regulation of oxidative DNA damage repair has been incompletely investigated. Moreover, in hyperglycemia the O-GlcNAc post-translational protein modification has been reported to interfere with the regular intracellular activity of metabolically relevant proteins in either an adaptive or a maladaptive manner. The enzyme 8-oxoguanosine DNA glycosylase (OGG1) is key in DNA repair. Thus, the objective of this work was to investigate the influence of O-GlcNAcylation of OGG1 in excessive glucose concentrations, simulating the levels observed in diabetic animals or humans. Neonatal cardiac myocytes (NCM) were isolated and cultured for 72 h in either normal glucose (NG; 5.5 mM glucose, 19.5 mM mannitol) or high glucose (HG; 25 mM glucose). The relationship between OGG1 O-GlcNAcylation levels, en...