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 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.
Division of Cardiovascular Science, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Hajime
H
Sato
Masafumi
M
Takahashi
Hirohiko
H
Ise
Ai
A
Yamada
Sho-ichi
S
Hirose
Yoh-ichi
Y
Tagawa
Hajime
H
Morimoto
Atsushi
A
Izawa
Uichi
U
Ikeda
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000196:embryology; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D012333:RNA, Messenger; C011669:ascorbate-2-phosphate; D003094:Collagen; D001205:Ascorbic Acid