TY - JOUR
T1 - Collagen synthesis is required for ascorbic acid-enhanced differentiation of mouse embryonic stem cells into cardiomyocytes
AU - Sato, Hajime
AU - Takahashi, Masafumi
AU - Ise, Hirohiko
AU - Yamada, Ai
AU - Hirose, Sho Ichi
AU - Tagawa, Yoh Ichi
AU - Morimoto, Hajime
AU - Izawa, Atsushi
AU - Ikeda, Uichi
N1 - Funding Information:
We thank Ryu-Ichiro Hata (Kanagawa Dental College) for helpful suggestion and Tomoko Hamaji, Junko Yano, and Kazuko Misawa for excellent technical assistance. This study was supported by research grants from the Ministry of Education, Science and Culture, the Ministry of Health, Labor and Welfare (#16590667 to M.T., and #16390220 to U.I.), and Mitsubishi Pharma Research Foundation (to M.T.).
PY - 2006/3/31
Y1 - 2006/3/31
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2006.01.116
DO - 10.1016/j.bbrc.2006.01.116
M3 - Article
C2 - 16480687
AN - SCOPUS:32644464702
SN - 0006-291X
VL - 342
SP - 107
EP - 112
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -