title: Curcumin induces differentiation of embryonic stem cells through possible modulation of nitric oxide-cyclic GMP pathway.
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.
authors: Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, TX 77030, USA. Kalpana.Mujoo@uth.tmc.edu
authors: Kalpana
authors: K
authors: Mujoo
authors: Lubov E
authors: LE
authors: Nikonoff
authors: Vladislav G
authors: VG
authors: Sharin
authors: Nathan S
authors: NS
authors: Bryan
authors: Alexander Y
authors: AY
authors: Kots
authors: Ferid
authors: F
authors: Murad
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D058732:Embryoid Bodies / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015290:Second Messenger Systems; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014336:Troponin / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D000975:Antioxidants; D020536:Enzyme Activators; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011720:Pyrazoles; D011725:Pyridines; C495901:TP53 protein, human; D014157:Transcription Factors; D014336:Troponin; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D018995:Myosin Heavy Chains; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D003474:Curcumin