scholarly journals A Short-Term Incubation with High Glucose Impairs VASP Phosphorylation at Serine 239 in response to the Nitric Oxide/cGMP Pathway in Vascular Smooth Muscle Cells: Role of Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Isabella Russo ◽  
Michela Viretto ◽  
Gabriella Doronzo ◽  
Cristina Barale ◽  
Luigi Mattiello ◽  
...  

A reduction of the nitric oxide (NO) action in vascular smooth muscle cells (VSMC) could play a role in the vascular damage induced by the glycaemic excursions occurring in diabetic patients; in this study, we aimed to clarify whether a short-term incubation of cultured VSMC with high glucose reduces the NO ability to increase cGMP and the cGMP ability to phosphorylate VASP at Ser-239. We observed that a 180 min incubation of rat VSMC with 25 mmol/L glucose does not impair the NO-induced cGMP increase but reduces VASP phosphorylation in response to both NO and cGMP with a mechanism blunted by antioxidants. We further demonstrated that high glucose increases radical oxygen species (ROS) production and that this phenomenon is prevented by the PKC inhibitor chelerythrine and the NADPH oxidase inhibitor apocynin. The following sequence of events is supported by these results: (i) in VSMC high glucose activates PKC; (ii) PKC activates NADPH oxidase; (iii) NADPH oxidase induces oxidative stress; (iv) ROS impair the signalling of cGMP, which is involved in the antiatherogenic actions of NO. Thus, high glucose, via oxidative stress, can reduce the cardiovascular protection conferred by the NO/cGMP pathway via phosphorylation of the cytoskeleton protein VASP in VSMC.

2008 ◽  
Vol 294 (6) ◽  
pp. H2845-H2854 ◽  
Author(s):  
Yuan Li ◽  
Magda Descorbeth ◽  
Madhu B. Anand-Srivastava

We have recently shown that aorta from streptozotocin (STZ)-induced diabetic rats and A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited decreased levels of inhibitory guanine nucleotide regulatory protein (Gi)α proteins. In the present studies, we investigated the implication of oxidative stress in the hyperglycemia/diabetes-induced decreased expression of the Giα protein and adenylyl cyclase signaling in VSMCs by using antioxidants. The levels of Giα proteins were significantly decreased 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. In addition, 111Mn-tetralis(benzoic acid porphyrin) and uric acid, scavengers of peroxynitrite, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase but not catalase, also restored the high glucose-induced decreased expression of Giα proteins to the control levels in A10 VSMCs. Furthermore, the enhanced production of superoxide anion (O2−) and increased activity of NADPH oxidase in these cells were also restored to control levels by diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, the diminished inhibition of adenylyl cyclase activity by inhibitory hormones and forskolin-stimulated adenylyl cyclase activity by low concentrations of GTPγS as well as the enhanced stimulation of adenylyl cyclase by stimulatory agonists in hyperglycemic cells were restored to control levels by antioxidant treatments. These results suggest that high glucose-induced decreased levels of Giα proteins and associated signaling in A10 VSMCs may be attributed to the enhanced oxidative stress due to augmented levels of peroxynitrite and not to H2O2.


2020 ◽  
Vol 11 (8) ◽  
pp. 6843-6854 ◽  
Author(s):  
Fang Wang ◽  
Zebin Weng ◽  
Yi Lyu ◽  
Yifan Bao ◽  
Juncheng Liu ◽  
...  

This study explores the antioxidative effect of a specific wheat germ-derived peptide on high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs) and the underlying mechanisms.


2015 ◽  
Vol 361 (2) ◽  
pp. 593-604 ◽  
Author(s):  
Adrian Manea ◽  
Simona-Adriana Manea ◽  
Andra Todirita ◽  
Irina Cristina Albulescu ◽  
Monica Raicu ◽  
...  

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