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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
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 reduce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981118/ https://www.ncbi.nlm.nih.gov/pubmed/24779009 http://dx.doi.org/10.1155/2014/328959 |
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author | Russo, Isabella Viretto, Michela Doronzo, Gabriella Barale, Cristina Mattiello, Luigi Anfossi, Giovanni Trovati, Mariella |
author_facet | Russo, Isabella Viretto, Michela Doronzo, Gabriella Barale, Cristina Mattiello, Luigi Anfossi, Giovanni Trovati, Mariella |
author_sort | Russo, Isabella |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3981118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-39811182014-04-28 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 Russo, Isabella Viretto, Michela Doronzo, Gabriella Barale, Cristina Mattiello, Luigi Anfossi, Giovanni Trovati, Mariella Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2014 2014-03-23 /pmc/articles/PMC3981118/ /pubmed/24779009 http://dx.doi.org/10.1155/2014/328959 Text en Copyright © 2014 Isabella Russo et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Russo, Isabella Viretto, Michela Doronzo, Gabriella Barale, Cristina Mattiello, Luigi Anfossi, Giovanni Trovati, Mariella 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3981118/ https://www.ncbi.nlm.nih.gov/pubmed/24779009 http://dx.doi.org/10.1155/2014/328959 |
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