Submitted on July 9, 2008
Revised on August 27, 2008
Accepted on September 18, 2008
High glucose increased the expression of Gq/11
and PLC
proteins and associated signaling in vascular smooth muscle cells
Magda Descorbeth1 and Madhu B Anand-Srivastava1*
1 University of Montreal
* To whom correspondence should be addressed. E-mail: madhu.anand-srivastava{at}umontreal.ca.
The levels and activity of protein kinase C (PKC) and diacylglycerol (DAG) were shown to be up-regulated in diabetes/hyperglycemia; however, studies on the expression of upstream signaling molecules of phosphatidyl inositol (PI) turnover were lacking. The present study was therefore undertaken to examine, if hyperglycemia/diabetes could also modulate the expression of Gq
and phospholipase Cb (PLC
) proteins and associated PI turnover signaling in aortic vascular smooth muscle cells (VSMC) and A10 VSMC exposed to high glucose. Aortic VSMC from STZ-diabetic rats exhibited an increased expression of Gq and PLC-1 proteins (60% and 30% respectively) as compared to control cells as determined by Western blotting. Pre-treatment of A10 VSMC with high glucose (26 mM) for 3 days also augmented the levels of Gq, G11, PLC-1 and -2 proteins by about 50, 35, 30 and 30 % respectively as compared to control cells which were restored to control levels by endothelin-1 (ET-1), ETA and ETB and angiotensin II (Ang II) AT1 receptor antagonists. In addition, ET-1-stimulated IP3 formation was also significantly higher in VSMC exposed to high glucose, whereas the basal levels of IP3 were not different between the two groups. Furthermore, treatment of A10 VSMC with Ang II and ET-1 also increased significantly the levels of Gq/11 and PLC proteins which were restored towards control levels by ETA/ETB and AT1 receptor antagonists. These results suggest that high glucose augmented the expression of Gq/11, PLC and -mediated signaling in VSMC which may be attributed to AT1, ETA and ETB receptors.
