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Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1

BACKGROUND: Creatine (Cr) is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that le...

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Autores principales: Braissant, Olivier, Henry, Hugues, Villard, Anne-Marie, Speer, Oliver, Wallimann, Theo, Bachmann, Claude
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175845/
https://www.ncbi.nlm.nih.gov/pubmed/15918910
http://dx.doi.org/10.1186/1471-213X-5-9
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author Braissant, Olivier
Henry, Hugues
Villard, Anne-Marie
Speer, Oliver
Wallimann, Theo
Bachmann, Claude
author_facet Braissant, Olivier
Henry, Hugues
Villard, Anne-Marie
Speer, Oliver
Wallimann, Theo
Bachmann, Claude
author_sort Braissant, Olivier
collection PubMed
description BACKGROUND: Creatine (Cr) is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that lead to Cr deficiency, neurological symptoms in early infancy and severe neurodevelopmental delay. To investigate the involvement of Cr synthesis and uptake pathways during embryonic development, we determined the spatiotemporal expression of AGAT, GAMT and CT1 during the rat embryogenesis, at the mRNA and protein level. RESULTS: We show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas. AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT. High levels of CT1 are found in epithelia. CONCLUSION: Our results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development. This work provides new clues on how creatine can be provided to developing tissues, and suggests that Cr deficiencies might induce irreversible damages already in utero, particularly on the nervous system.
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spelling pubmed-11758452005-07-16 Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1 Braissant, Olivier Henry, Hugues Villard, Anne-Marie Speer, Oliver Wallimann, Theo Bachmann, Claude BMC Dev Biol Research Article BACKGROUND: Creatine (Cr) is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that lead to Cr deficiency, neurological symptoms in early infancy and severe neurodevelopmental delay. To investigate the involvement of Cr synthesis and uptake pathways during embryonic development, we determined the spatiotemporal expression of AGAT, GAMT and CT1 during the rat embryogenesis, at the mRNA and protein level. RESULTS: We show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas. AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT. High levels of CT1 are found in epithelia. CONCLUSION: Our results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development. This work provides new clues on how creatine can be provided to developing tissues, and suggests that Cr deficiencies might induce irreversible damages already in utero, particularly on the nervous system. BioMed Central 2005-05-26 /pmc/articles/PMC1175845/ /pubmed/15918910 http://dx.doi.org/10.1186/1471-213X-5-9 Text en Copyright © 2005 Braissant et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Braissant, Olivier
Henry, Hugues
Villard, Anne-Marie
Speer, Oliver
Wallimann, Theo
Bachmann, Claude
Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title_full Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title_fullStr Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title_full_unstemmed Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title_short Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
title_sort creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of agat, gamt and ct1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175845/
https://www.ncbi.nlm.nih.gov/pubmed/15918910
http://dx.doi.org/10.1186/1471-213X-5-9
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