Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Pressler Street, Houston, TX 77030, USA.
Protein Cell. 2012 Jul;3(7):535-44. doi: 10.1007/s13238-012-2053-2. Epub 2012 Jul 10.
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.
姜黄素是咖喱中使用的一种膳食香料的活性成分，已被证明具有抗氧化、抗炎和抗增殖特性。使用 EB 定向分化方案的 H-9 人胚胎干细胞 (ES) 细胞；我们评估了姜黄素 (0-20 μmol/L) 在增强这种分化中的作用。我们使用实时 PCR、western blot 和免疫染色的结果表明，姜黄素在 ES 细胞分化过程中显著增加了心脏特异性转录因子 NKx2.5、心肌肌钙蛋白 I、肌球蛋白重链和内皮型一氧化氮合酶的基因表达和蛋白水平。此外，一氧化氮供体增强了姜黄素介导的 NKx2.5 和其他心脏特异性蛋白的诱导。细胞孵育姜黄素导致细胞内亚硝酸盐的剂量依赖性增加，与给予真正的一氧化氮供体相同。第二信使 (cAMP) 和环鸟苷酸 (cGMP) 的功能测定表明，在分化细胞中连续存在姜黄素会降低 cAMP 的基线水平，但会显著升高 cGMP 的基线含量。姜黄素添加到无细胞测定中可显著抑制提取物中 cAMP 和 cGMP 的降解，而长期用姜黄素处理完整细胞会增加 cAMP 和 cGMP 的降解率，这表明这可能是由于姜黄素直接抑制某些环核苷酸降解酶 (磷酸二酯酶)。这些研究表明，多酚姜黄素可能参与 ES 细胞的分化，部分原因是其对一氧化氮信号的操纵。
