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Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)

(1) Background: Tissue non-specific alkaline phosphatase (TNAP) is suspected to induce atherosclerosis plaque calcification. TNAP, during physiological mineralization, hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PP(i)). Since atherosclerosis plaques are characterized by the pres...

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Autores principales: Buchet, Rene, Tribes, Camille, Rouaix, Valentine, Doumèche, Bastien, Fiore, Michele, Wu, Yuqing, Magne, David, Mebarek, Saida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000465/
https://www.ncbi.nlm.nih.gov/pubmed/33799449
http://dx.doi.org/10.3390/ijms22062948
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author Buchet, Rene
Tribes, Camille
Rouaix, Valentine
Doumèche, Bastien
Fiore, Michele
Wu, Yuqing
Magne, David
Mebarek, Saida
author_facet Buchet, Rene
Tribes, Camille
Rouaix, Valentine
Doumèche, Bastien
Fiore, Michele
Wu, Yuqing
Magne, David
Mebarek, Saida
author_sort Buchet, Rene
collection PubMed
description (1) Background: Tissue non-specific alkaline phosphatase (TNAP) is suspected to induce atherosclerosis plaque calcification. TNAP, during physiological mineralization, hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PP(i)). Since atherosclerosis plaques are characterized by the presence of necrotic cells that probably release supraphysiological concentrations of ATP, we explored whether this extracellular adenosine triphosphate (ATP) is hydrolyzed into the mineralization inhibitor PP(i) or the mineralization stimulator inorganic phosphate (P(i)), and whether TNAP is involved. (2) Methods: Murine aortic smooth muscle cell line (MOVAS cells) were transdifferentiated into chondrocyte-like cells in calcifying medium, containing ascorbic acid and β-glycerophosphate. ATP hydrolysis rates were determined in extracellular medium extracted from MOVAS cultures during their transdifferentiation, using (31)P-NMR and IR spectroscopy. (3) Results: ATP and PP(i) hydrolysis by MOVAS cells increased during transdifferentiation. ATP hydrolysis was sequential, yielding adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine without any detectable PP(i). The addition of levamisole partially inhibited ATP hydrolysis, indicating that TNAP and other types of ectonucleoside triphoshatediphosphohydrolases contributed to ATP hydrolysis. (4) Conclusions: Our findings suggest that high ATP levels released by cells in proximity to vascular smooth muscle cells (VSMCs) in atherosclerosis plaques generate P(i) and not PP(i), which may exacerbate plaque calcification.
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spelling pubmed-80004652021-03-28 Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i) Buchet, Rene Tribes, Camille Rouaix, Valentine Doumèche, Bastien Fiore, Michele Wu, Yuqing Magne, David Mebarek, Saida Int J Mol Sci Article (1) Background: Tissue non-specific alkaline phosphatase (TNAP) is suspected to induce atherosclerosis plaque calcification. TNAP, during physiological mineralization, hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PP(i)). Since atherosclerosis plaques are characterized by the presence of necrotic cells that probably release supraphysiological concentrations of ATP, we explored whether this extracellular adenosine triphosphate (ATP) is hydrolyzed into the mineralization inhibitor PP(i) or the mineralization stimulator inorganic phosphate (P(i)), and whether TNAP is involved. (2) Methods: Murine aortic smooth muscle cell line (MOVAS cells) were transdifferentiated into chondrocyte-like cells in calcifying medium, containing ascorbic acid and β-glycerophosphate. ATP hydrolysis rates were determined in extracellular medium extracted from MOVAS cultures during their transdifferentiation, using (31)P-NMR and IR spectroscopy. (3) Results: ATP and PP(i) hydrolysis by MOVAS cells increased during transdifferentiation. ATP hydrolysis was sequential, yielding adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine without any detectable PP(i). The addition of levamisole partially inhibited ATP hydrolysis, indicating that TNAP and other types of ectonucleoside triphoshatediphosphohydrolases contributed to ATP hydrolysis. (4) Conclusions: Our findings suggest that high ATP levels released by cells in proximity to vascular smooth muscle cells (VSMCs) in atherosclerosis plaques generate P(i) and not PP(i), which may exacerbate plaque calcification. MDPI 2021-03-14 /pmc/articles/PMC8000465/ /pubmed/33799449 http://dx.doi.org/10.3390/ijms22062948 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buchet, Rene
Tribes, Camille
Rouaix, Valentine
Doumèche, Bastien
Fiore, Michele
Wu, Yuqing
Magne, David
Mebarek, Saida
Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title_full Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title_fullStr Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title_full_unstemmed Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title_short Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates P(i) but Not PP(i)
title_sort hydrolysis of extracellular atp by vascular smooth muscle cells transdifferentiated into chondrocytes generates p(i) but not pp(i)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000465/
https://www.ncbi.nlm.nih.gov/pubmed/33799449
http://dx.doi.org/10.3390/ijms22062948
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