The effects of hyperglycemia and angiotensin II on methylglyoxal and glyoxalase 1 in primary vascular smooth muscle cells

Objective: Ang II is suggested to enhance cellular MGO levels, a glycolysis by-product and elevated concentrations determined in diabetics, by suppressing MGO detoxifying Glo1 enzyme expression. For this purpose, effects of Ang II on Glo1 activity and expression, GSH concentration, MGO level, NF-κB p65 expression, and S536 phosphorylation in addition to Nrf2 expression levels were investigated under low and high glucose conditions in vascular smooth muscle cells (VSMCs). Moreover, impact of Ang II-induced NF-κB, p38 and ERK1/2 MAPK activations on Glo1 expression and activity were explored. Method: VSMCs were isolated from rat aorta and primarily cultured. Ang II-treated cells (100 nM) were incubated 48 hours under low and high glucose media, and then measurements were done in obtained cell lysates. Results: Ang II increased MGO levels by suppressing Glo1 activity and expression under low and high glucose media, while telmisartan and irbesartan treatment abolished Ang II's effects. It is likely that p38 MAPK and NF-κB pathways play role in Ang II-induced reduction in Glo1 expression. High glucose also elevated MGO levels and contributed to the attenuation of Glo1 expression via p38 MAPK and NF-κB pathways activation. Besides, Ang II in low glucose media and apart from it, high glucose elevates Nrf2 expression, p38 and ERK1/2 MAPK activations seem play a role in this elevation. Conclusion: Though Ang II may induce Nrf2 elevation, in low glucose media it may decrease Glo1 expression through p38 MAPK and NF-κB activations, and raise MGO levels in this way. MGO is shown to upregulate RAS associated with hypertension. This study suggests that RAS effector peptide Ang II could display a hyperglycemia-like effect by enhancing MGO concentration. Key words: vdkh, ang II, glo1, mgo, nrf2