O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation

Effect of an aqueous extract of Cucurbita ficifolia Bouché on the glutathione redox cycle in mice with STZ-induced diabetes

“…According with the first two possibilities Jiao et al (2007) found an increase in GPx in liver of mice with a mild state of diabetes. The enhanced GPx and GR activities found in this study could be due to a compensatory mechanism as a response of mild increase of oxidative stress or hyperglycemia or both; since GPx activation can be induced by hyperglycemia in a mechanism mediated by O-GlcNAcylation (Yang et al, 2010), in a higher oxidative stress condition, the accumulated oxidative damage could reduce the activities of these enzymes. Regardless of having high activities of GPx and GR, often GSH concentrations were depleted, this failure can be, at least in part attributed to a diminished supply of NADPH, required by the regeneration of GSH, because of decreased activity of glucose-6-phosphate dehydrogenase (G6PDH) (Xu et al, 2005;Díaz-Flores et al, 2006. The group that received C. ficifolia reestablished GPx and GR activities in liver, pancreas and kidney, reaching similar levels to normal controls.…”

“…Regardless of having high activities of GPx and GR, often GSH concentrations were depleted, this failure can be, at least in part attributed to a diminished supply of NADPH, required by the regeneration of GSH, because of decreased activity of glucose-6-phosphate dehydrogenase (G6PDH) (Xu et al, 2005;Díaz-Flores et al, 2006. The group that received C. ficifolia reestablished GPx and GR activities in liver, pancreas and kidney, reaching similar levels to normal controls. It is possible that when ROS and hyperglycemia are reduced by treatment with the C. ficifolia extract, the activity of enzymes of redox pathway of GSH, specially GPX, also can to be reduced; since GPx was induced by hyperglycemia in diabetic animals (Yang et al, 2010), and also was decreased in the mice treated with pioglitazone. Additional studies are requires for analyze the participation of G6PDH and g-glutamyl cysteinyl ligase in the changes of components of glutathione system induced by diabetes and C. ficifolia.…”

Protein O-GlcNAcylation regulates Drosophila growth through the insulin signaling pathway

“…Treatment with insulin-like growth factor-1 increases both phosphorylation and O-GlcNAcylation of Akt1 in SH-SY5Y neuroblastoma cells [8]. Studies on glutathione peroxidase 1 (GPX1) under hyperglycemic conditions suggest that O-GlcNAcylation on GPX1 increases GPX1 phosphorylation and consequently enhances the activity of the protein [26]. To better understand the significance of Akt O-GlcNAcylation, further investigations, including identification and manipulation of O-GlcNAc modification sites, are warranted.…”

Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle

“…Impaired O-GlcNAc cycling has been associated with insulin resistance [20] and muscle atrophy [22]. There have been reports demonstrating a link between O-GlcNAcylation and redox signaling, with several ROS-responsive enzymes recognized to be O-GlcNAc modified [12,14,23]. The interaction could represent one of the mechanisms underlying cellular adaptation to oxidative stress.…”

“…O-GlcNAcylation has been suggested to play roles in various processes, including the cellular response to stress [11]. O-GlcNAc binds to several transcription factors [12], HSPs [13] and antioxidant enzymes [14,15], modulating their expression, stability, and function. Furthermore, it is involved in regulation of protein homeostasis [16], participates in cellular immune response [17] and DNA repair [18].…”