Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells.
We have recently shown that aortic vascular smooth muscle cells (VSMCs) from streptozotocin (STZ)-induced diabetic rats and A10 VSMCs exposed to high glucose exhibited increased levels of Gqα and PLCβ proteins. In the present study, we investigated whether the enhanced oxidative stress in hyperglycemia/diabetes contributes to the increased expression of the Gq/11α and PLCβ proteins and the associated signaling in VSMCs by using antioxidants. The levels of Gq/11α and PLCβ1/2 proteins, as determined by Western blotting, were significantly increased in A10 VSMCs exposed to high glucose and in aortic VSMCs from STZ-diabetic rats compared with control cells and were restored to control levels by antioxidants: apocynin, an NADPH oxidase inhibitor, and catalase, a scavenger of hydrogen peroxide. However, (111)Mn-tetrakis(benzoic acid porphyrin) and uric acid, scavengers of peroxynitrite, did not affect the high-glucose-induced enhanced levels of Gq/11α and PLCβ proteins in A10 cells. Furthermore, the levels of superoxide dismutase-1 (SOD-1) but not of SOD-2 protein were augmented by high glucose. In addition, high-glucose-induced endothelin-1-stimulated production of IP(3) was also restored toward control levels by catalase. These results suggest that hyperglycemia/diabetes-induced enhanced expression of Gq/11α and PLCβ proteins and signaling may be attributable to the enhanced oxidative stress due to augmented levels of H(2)O(2) and not to peroxynitrite.
Descorbeth
Magda
M
Department of Physiology, Faculty of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada.
Anand-Srivastava
Madhu B
MB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013311:Streptozocin / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
D000975:Antioxidants; D013311:Streptozocin; D006861:Hydrogen Peroxide; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005947:Glucose