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Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta
S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide ((•)NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat ao...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439434/ https://www.ncbi.nlm.nih.gov/pubmed/22984412 http://dx.doi.org/10.1371/journal.pone.0043190 |
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author | Dahboul, Fatima Leroy, Pierre Maguin Gate, Katy Boudier, Ariane Gaucher, Caroline Liminana, Patrick Lartaud, Isabelle Pompella, Alfonso Perrin-Sarrado, Caroline |
author_facet | Dahboul, Fatima Leroy, Pierre Maguin Gate, Katy Boudier, Ariane Gaucher, Caroline Liminana, Patrick Lartaud, Isabelle Pompella, Alfonso Perrin-Sarrado, Caroline |
author_sort | Dahboul, Fatima |
collection | PubMed |
description | S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide ((•)NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), (•)NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free (•)NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2±0.5.10(−7) M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6±0.2.10(−6) M) and acivicin (8.3±0.6.10(−7) M), while it decreased with glycylglycine (4.7±0.9.10(−8) M). In endothelium-denuded aorta, EC(50) for GSNO alone increased to 2.3±0.3.10(−6) M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective. |
format | Online Article Text |
id | pubmed-3439434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34394342012-09-14 Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta Dahboul, Fatima Leroy, Pierre Maguin Gate, Katy Boudier, Ariane Gaucher, Caroline Liminana, Patrick Lartaud, Isabelle Pompella, Alfonso Perrin-Sarrado, Caroline PLoS One Research Article S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide ((•)NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), (•)NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free (•)NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2±0.5.10(−7) M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6±0.2.10(−6) M) and acivicin (8.3±0.6.10(−7) M), while it decreased with glycylglycine (4.7±0.9.10(−8) M). In endothelium-denuded aorta, EC(50) for GSNO alone increased to 2.3±0.3.10(−6) M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective. Public Library of Science 2012-09-11 /pmc/articles/PMC3439434/ /pubmed/22984412 http://dx.doi.org/10.1371/journal.pone.0043190 Text en © 2012 Dahboul et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Dahboul, Fatima Leroy, Pierre Maguin Gate, Katy Boudier, Ariane Gaucher, Caroline Liminana, Patrick Lartaud, Isabelle Pompella, Alfonso Perrin-Sarrado, Caroline Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title | Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title_full | Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title_fullStr | Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title_full_unstemmed | Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title_short | Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta |
title_sort | endothelial γ-glutamyltransferase contributes to the vasorelaxant effect of s-nitrosoglutathione in rat aorta |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439434/ https://www.ncbi.nlm.nih.gov/pubmed/22984412 http://dx.doi.org/10.1371/journal.pone.0043190 |
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