Ascorbic acid drives the differentiation of mesoderm-derived embryonic stem cells. Involvement of p38 MAPK/CREB and SVCT2 transporter.
Mol Nutr Food Res
; 61(5)2017 05.
Article
em En
| MEDLINE
| ID: mdl-27957816
ABSTRACT
SCOPE Here we tested the hypothesis that ascorbic acid (AA) is a signaling molecule acting on stem cells via the differentiation of mesoderm derivatives, including myocytes, osteocytes, and adipocytes. MATERIAL AND METHODS:
Investigations used a murine embryonic stem cell line CGR8 able to differentiate into different cell types and treated or not with ascorbic acid. Differentiation was tracked mainly through cellular anatomy (including presence of beating cardiomyocytes) and expression of specific markers.CONCLUSION:
The study demonstrated that AA drives mesoderm-derived stem cell differentiation toward myogenesis and osteogenesis and also inhibits adipogenesis. Further experiments found that AA competes with retinoic acid (RA) to drive cell differentiation in a dose-dependent manner AA inhibited neurogenic differentiation and stimulated myogenesis whereas RA did the reverse. The AA-dependent differentiation of embryonic stem cells was shown to involve a p38 MAPK/CREB pathway, probably stimulated by cAMP via adenylate cyclases. In addition, SVCT2, the intracellular transporter of AA, acted as a receptor. Finally, we showed that activation/repression of specific differentiation markers is associated with epigenetic changes in their associated promoters. We discuss the impact of these findings in terms of obesity and aging.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Ascórbico
/
Proteínas Quinases p38 Ativadas por Mitógeno
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Proteína de Ligação a CREB
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Células-Tronco Embrionárias
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Transportadores de Sódio Acoplados à Vitamina C
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Mesoderma
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article