Papel da O-Glicosilação com N-Acetil-Glucosamina (O-GlcNAc) nas alterações vasculares via modulação de fatores imunológicos

Abstract

The control of vascular tone is regulated by vascular smooth muscle cells and various humoral factors such as Angiotensin II, prostaglandins, endothelin-1, cytokines, among others. O-Glycosylation N-acetyl-glucosamine (O-GlcNAc) is a reversible post-translational modification mediated by two enzymes O-GlcNAcase and O-GlcNAc transferase. Recent studies suggest that O-GlcNAc may be involved in the contractile properties of the vascular smooth musculature. There is evidence that high levels of O-GlcNAc are associated with increased vasoconstriction and, in addition, it is noted that the increased levels of glycated proteins with O-GlcNAc is capable of reducing the nitric oxide synthase expression, impairing vasodilation . Additionally, it was observed that modulation of reactive oxygen species (ROS) promote vascular dysfunction characterized by increased contraction and relaxation decrease in vascular smooth muscle cells. Thus, we tested the hypothesis that increased levels of protein O-GlcNAc, resulting in the production of ROS contributing to vascular dysfunction. The aortic segments (from Wistar rats) incubated with PUGNAc for 12 hours and submitted to Dihydroethidine assay showed increased production of superoxide anion, compared with the control group. The origin of the superoxide anion, in our study, was increased due to increased protein expression of enzymes Nox-1 and Nox-4 involved in superoxide anion production in vascular cells. Through vascular relaxation study endothelium-dependent, we evaluated aortas treated with vehicle and PUGNAc and the presence or absence of apocynin and Tiron. It was observed decreasing the relaxation ability of the aorta treated with PUGNAc compared to vehicle. There was an increase in gene and protein expression of TNF-α and TNF-α receptor in aortas treated with PUGNAc for 6 hours, compared to the vehicle group. In aortas treated with PUGNAc for 12 hours, we observed a decrease of the evaluation of protein expression of TGF-β compared to the vehicle group. It is concluded that the induction of O-GlcNAc by incubating with PUGNAc, was capable of inducing the production of ROS, and some cases of pro-inflammatory cytokines, and therefore trigger vascular disorder characterized by a reduced relaxation endotheliumdependent these aortas.