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Published on: June 3, 2018
Ascorbic acid rescues cardiomyocyte development in Fgfr1(-/-) murine embryonic stem cells
Elisabetta Crescini1, Laura Gualandi, Daniela Uberti
1Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy.
Biochimica Et Biophysica Acta
|June 28, 2012
Summary
L-ascorbic acid, a form of vitamin C, rescued cardiomyocyte differentiation in Fgfr1 knockout stem cells. This effect was linked to hypoxia-inducible factor (HIF)-1α modulation, not antioxidant properties.
Area of Science:
- Stem Cell Biology
- Developmental Biology
- Molecular Cardiology
Background:
- Fibroblast growth factor receptor 1 (Fgfr1) is crucial for cardiomyocyte differentiation in murine embryonic stem cells (mESC).
- Fgfr1 deficiency severely impairs the cardiomyogenic potential of mESC.
Purpose of the Study:
- To investigate chemical compounds that can rescue cardiomyocyte differentiation in Fgfr1 knockout mESC.
- To elucidate the mechanism by which l-ascorbic acid (vitamin C) promotes cardiomyogenesis in Fgfr1-deficient mESC.
Main Methods:
- Screening of chemical compounds, including vitamin C, for their ability to restore cardiomyocyte formation in Fgfr1(-/-) mESC.
- Analysis of intracellular redox state parameters (ROS, Nox4, SOD) and pluripotency gene expression.
- Investigation of the role of prolyl hydroxylase activity and hypoxia-inducible factor (HIF)-1α signaling.
Main Results:
- L-ascorbic acid, but not other tested compounds, effectively rescued beating cardiomyocyte differentiation in Fgfr1(-/-) mESC.
- Vitamin C's rescue effect was independent of its antioxidant capacity or modulation of pluripotency genes.
- Fe(2+) and a HIF inhibitor (CAY10585) mimicked vitamin C's rescue effect, correlating with slightly upregulated HIF-1α in Fgfr1(-/-) cells.
Conclusions:
- L-ascorbic acid promotes Fgfr1-dependent cardiomyocyte differentiation in mESC.
- The mechanism involves modulating HIF-1α signaling, potentially by acting as a prolyl hydroxylase cofactor, rather than through antioxidant effects.
- HIF-1α is a key mediator in Fgfr1-regulated cardiomyogenesis.
