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p53 POST-TRANSLATIONAL MODIFICATIONS AS MARKERS IN THE DIAGNOSIS AND PROGNOSIS OF A NEURODEGENERATIVE DISEASE
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Ascorbic acid rescues cardiomyocyte development in Fgfr1(-/-) murine embryonic stem cells.
No full textFibroblast growth factor receptor 1 (Fgfr1) gene knockout impairs cardiomyocyte differentiation in murine
embryonic stem cells (mESC). Here, various chemical compounds able to enhance cardiomyocyte differentiation
in mESC [including dimethylsulfoxide, ascorbic acid (vitC), free radicals and reactive oxygen species]
were tested for their ability to rescue the cardiomyogenic potential of Fgfr1−/− mESC. Among them, only
the reduced form of vitC, L-ascorbic acid, was able to recover beating cell differentiation in Fgfr1−/− mESC.
The appearance of contracting cells was paralleled by the expression of early and late cardiac gene markers,
thus suggesting their identity as cardiomyocytes. In the attempt to elucidate the mechanism of action of vitC
on Fgfr1−/− mESC, we analyzed several parameters related to the intracellular redox state, such as reactive
oxygen species content, Nox4 expression, and superoxide dismutase activity. The results did not show any relationship
between the antioxidant capacity of vitC and cardiomyocyte differentiation in Fgfr1−/− mESC. No
correlation was found also for the ability of vitC to modulate the expression of pluripotency genes. Then, we
tested the hypothesis that vitC was acting as a prolyl hydroxylase cofactor by maintaining iron in a reduced
state. We first analyze hypoxia inducible factor (HIF)-1α mRNA and protein levels that were found to be
slightly upregulated in Fgfr1−/− cells. We treated mESC with Fe2+ or the HIF inhibitor CAY10585 during the
first phasesof thedifferentiationprocessand, similar tovitC, the twocompoundswereable to rescue cardiomyocyte
formation in Fgfr1−/− mESC, thus implicating HIF-1α modulation in Fgfr1-dependent cardiomyogenesis
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