Acebutolol Attenuates Glycoxidative Stress and Alters mTOR-Associated Phosphoprotein Signaling in Hyperglycemic HUVECs

Hyperglycemia promotes endothelial glycoxidative stress and is accompanied by alterations in intracellular signaling. This study investigated whether acebutolol attenuates hyperglycemia-induced glycoxidative injury and alters the phosphorylation of proteins associated with PI3K/Akt/mTOR signaling in human umbilical vein endothelial cells (HUVECs). HUVECs were cultured for 7 days under hyperglycemic conditions induced by 30 mM D-glucose and treated with acebutolol at concentrations of 20–100 μg/mL. Glycation- and glycoxidation-related endpoints, protein oxidation, oxidative stress, caspase-3 activity, and phosphorylation of eight signaling proteins were assessed. Data were normalized to the hyperglycemic control and analyzed using one-way ANOVA followed by Dunnett’s test. At 100 μg/mL, acebutolol significantly reduced markers of glycation, glycoxidation, protein oxidation, and oxidative stress by 23–41% (p < 0.05), including total advanced glycation end products (AGEs), argpyrimidine, pentosidine, N-formylkynurenine, advanced oxidation protein products, amyloid cross-β structures, and NADPH oxidase activity. Caspase-3 activity was not significantly increased. At 20–80 μg/mL, acebutolol significantly altered the phosphorylation of several proteins associated with PI3K/Akt/mTOR signaling. The most pronounced effects were observed for p-S6RP, p-mTOR, p-BAD, and p-IRS1, whose relative phosphorylation signals decreased to 0.7–21.4% of the hyperglycemic control, defined as 100%. Significant reductions were also observed for p-GSK3α/β, p-p70S6K, and p-PTEN, whereas p-Akt was not significantly affected. At 100 μg/mL, reductions in several phosphoproteins were less pronounced than at lower concentrations, indicating a non-monotonic response pattern. Overall, acebutolol attenuated hyperglycemia-associated glycoxidative injury and altered the phosphorylation profile of proteins associated with PI3K/Akt/mTOR signaling in endothelial cells.