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Pyruvate antioxidant roles in human fibroblasts and embryonic stem cells

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Abstract

Oxidative stress has been related to multiple diseases, especially during early embryonic development, when environmental alterations can lead to long-term deleterious effects. In vitro studies of oxidative stress have been mainly focused on somatic cells, but embryonic stem cells (ESCs) represent a promising model of early embryonic development as they are the in vitro equivalent to pluripotent cells in the embryo. Human fibroblasts and ESCs were exposed to different pro-oxidant agents (hydrogen peroxide, tert-butyl hydroperoxide (TBHP), and rotenone) and antioxidants (sodium pyruvate, N-acetylcysteine, Trolox, and sodium selenite) during a 72 h oxidative stress treatment. Then, cell viability, oxidative stress, mitochondrial activity, and gene expression were analyzed, focusing on the antioxidant effect of pyruvate. Pyruvate protected both somatic and pluripotent cells against different pro-oxidant agents, showing strong ROS scavenging capacity, protecting mitochondrial membrane potential, and regulating gene expression and cell metabolism through different mechanisms in fibroblasts and ESCs. In fibroblasts, pyruvate avoided NFKβ nuclear translocation and the upregulation of genes related to the oxidative stress response, while in ESCs pyruvate stimulated the expression of genes involved in anaerobic glycolysis. Fibroblasts and ESCs reacted in different ways to oxidative stress and antioxidant treatment, and pyruvate was the most complete antioxidant, protecting both cell types at different levels.

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Acknowledgements

HUES3 cells were kindly provided by D. Melton from Harvard Stem Cells Institute under specific Material Transfer Agreement to our colleague Cesare Galli. The technical support of Gabriella Crotti and Paola Turini is greatly acknowledged. This work was supported by EpiHealthNet Marie Curie ITN Project No 317146-FP7-People-2012-ITN and Epihealth Project EU FP7 No 278418. PRI and MB are fellows of the EpiHealthNet project.

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  1. Avantea, Laboratory of Reproductive Technologies, 26100, Cremona, Italy

    Priscila Ramos-Ibeas, Maria Barandalla, Silvia Colleoni & Giovanna Lazzari

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  1. Priscila Ramos-Ibeas
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  2. Maria Barandalla
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Correspondence to Priscila Ramos-Ibeas.

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Ramos-Ibeas, P., Barandalla, M., Colleoni, S. et al. Pyruvate antioxidant roles in human fibroblasts and embryonic stem cells. Mol Cell Biochem 429, 137–150 (2017). https://doi.org/10.1007/s11010-017-2942-z

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