Collagen synthesis is required for ascorbic acid-enhanced differentiation of mouse embryonic stem cells into cardiomyocytes

Ascorbic acid has been reported to promote the differentiation of embryonic stem (ES) cells into cardiomyocytes; however, the specific functions of ascorbic acid have not been defined. A stable form of ascorbic acid, namely, l-ascorbic acid 2-phosphate (A2-P), significantly enhanced cardiac differen...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-03, Vol.342 (1), p.107-112
Main Authors: Sato, Hajime, Takahashi, Masafumi, Ise, Hirohiko, Yamada, Ai, Hirose, Sho-ichi, Tagawa, Yoh-ichi, Morimoto, Hajime, Izawa, Atsushi, Ikeda, Uichi
Format: Article
Language:English
Subjects:
Animals
Antioxidants - pharmacology
Ascorbic acid
Ascorbic Acid - analogs & derivatives
Ascorbic Acid - pharmacology
Biomarkers
Cell Differentiation - drug effects
Cell Line
Collagen - antagonists & inhibitors
Collagen - biosynthesis
Differentiation
Extracellular matrix
Gene Expression Regulation - drug effects
Heart - drug effects
Heart - embryology
Mice
Myocardium
Myocytes, Cardiac - cytology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
RNA, Messenger - drug effects
Stem cell
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
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Summary:Ascorbic acid has been reported to promote the differentiation of embryonic stem (ES) cells into cardiomyocytes; however, the specific functions of ascorbic acid have not been defined. A stable form of ascorbic acid, namely, l-ascorbic acid 2-phosphate (A2-P), significantly enhanced cardiac differentiation; this was assessed by spontaneous beating of cardiomyocytes and expression of cardiac-specific markers obtained from mouse ES cells. This effect of ascorbic acid was observed only when A2-P was present during the early phase of differentiation. Treatment with two types of collagen synthesis inhibitors, l-2-azetidine carboxylic acid and cis-4-hydroxy-d-proline, significantly inhibited the A2-P-enhanced cardiac differentiation, whereas treatment with the antioxidant N-acetyl cysteine showed no effect. These findings demonstrated that ascorbic acid enhances differentiation of ES cells into cardiomyocytes through collagen synthesis and suggest its potential in the modification of cardiac differentiation of ES cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.01.116