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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...

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Autores principales: Dahboul, Fatima, Leroy, Pierre, Maguin Gate, Katy, Boudier, Ariane, Gaucher, Caroline, Liminana, Patrick, Lartaud, Isabelle, Pompella, Alfonso, Perrin-Sarrado, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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