Protein & Cell

, Volume 3, Issue 7, pp 535–544

Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway

Authors

    • Texas Therapeutics Institute, Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at Houston
  • Lubov E. Nikonoff
    • Texas Therapeutics Institute, Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at Houston
  • Vladislav G Sharin
    • Departments of Immunology and PathologyBaylor College of Medicine
  • Nathan S. Bryan
    • Texas Therapeutics Institute, Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at Houston
  • Alexander Y. Kots
    • Departments of Biochemistry and Molecular BiologyGeorge Washington University
  • Ferid Murad
    • Departments of Biochemistry and Molecular BiologyGeorge Washington University
Research Article

DOI: 10.1007/s13238-012-2053-2

Cite this article as:
Mujoo, K., Nikonoff, L.E., Sharin, V.G. et al. Protein Cell (2012) 3: 535. doi:10.1007/s13238-012-2053-2
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Abstract

Curcumin, an active ingredient of dietary spice used in curry, has been shown to exhibit anti-oxidant, anti-inflammatory and anti-proliferative properties. Using EB directed differentiation protocol of H-9 human embryonic stem (ES) cells; we evaluated the effect of curcumin (0–20 μmol/L) in enhancing such differentiation. Our results using real time PCR, western blotting and immunostaining demonstrated that curcumin significantly increased the gene expression and protein levels of cardiac specific transcription factor NKx2.5, cardiac troponin I, myosin heavy chain, and endothelial nitric oxide synthase during ES cell differentiation. Furthermore, an NO donor enhanced the curcumin-mediated induction of NKx2.5 and other cardiac specific proteins. Incubation of cells with curcumin led to a dose dependent increase in intracellular nitrite to the same extent as giving an authentic NO donor. Functional assay for second messenger(s) cyclic AMP (cAMP) and cyclic GMP (cGMP) revealed that continuous presence of curcumin in differentiated cells induced a decrease in the baseline levels of cAMP but it significantly elevated baseline contents of cGMP. Curcumin addition to a cell free assay significantly suppressed cAMP and cGMP degradation in the extracts while long term treatment of intact cells with curcumin increased the rates of cAMP and cGMP degradation suggesting that this might be due to direct suppression of some cyclic nucleotide-degrading enzyme (phosphodiesterase) by curcumin. These studies demonstrate that polyphenol curcumin may be involved in differentiation of ES cells partly due to manipulation of nitric oxide signaling.

Keywords

curcuminnitric oxidecyclic GMPembryonic stem cells

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012