High glucose increases the expression of Gq/11alpha and PLC-beta proteins and associated signaling in vascular smooth muscle cells.

The levels and activity of protein kinase C and diacylglycerol were shown to be upregulated in diabetes/hyperglycemia; however, studies on the expression of upstream signaling molecules of phosphatidylinositol turnover were lacking. The present study was therefore undertaken to examine whether hyperglycemia/diabetes could also modulate the expression of Gqalpha and phospholipase C-beta (PLC-beta) proteins and associated phosphatidylinositol turnover signaling in aortic vascular smooth muscle cells (VSMCs) and A10 VSMCs exposed to high glucose. Aortic VSMCs from streptozotocin-diabetic rats exhibited an increased expression of Gqalpha and PLC-beta1 proteins (60% and 30%, respectively) compared with control cells as determined by Western blot analysis. The pretreatment of A10 VSMCs with high glucose (26 mM) for 3 days also augmented the levels of Gqalpha, G11alpha, PLC-beta1 and -beta2 proteins by about 50, 35, 30, and 30%, respectively, compared with control cells that were restored to control levels by endothelin-1 (ET-1), ET types A and B (ET(A) and ET(B)) receptors, and angiotensin II type 1 (AT1) receptor antagonists. In addition, ET-1-stimulated inositol triphosphate formation was also significantly higher in VSMCs exposed to high glucose, whereas the basal levels of inositol triphosphate were not different between the two groups. Furthermore, the treatment of A10 VSMCs with angiotensin II and ET-1 also significantly increased the levels of Gq/11alpha and PLC-beta proteins that were restored toward control levels by ET(A)/ET(B) and AT1 receptor antagonists. These results suggest that high glucose augments the expression of Gq/11alpha, PLC-beta, and mediated signaling in VSMCs, which may be attributed to AT1, ET(A), and ET(B) receptors.

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