Natural Polyphenols Inhibit Lysine-Specific Demethylase-1 in vitro.
Natural Polyphenols Inhibit Lysine-Specific Demethylase-1 in vitro.
复制标题
DOI：
--
复制
发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
A. Abdulla;Xiaoping Zhao;Fajun Yang
中科院分区：
文献类型：
--
作者：
A. Abdulla;Xiaoping Zhao;Fajun Yang
天然多酚，如白藜芦醇，对癌症、糖尿病、心血管疾病等重大人类疾病有有益作用。除了作为抗氧化剂，其中一些多酚还可以靶向蛋白质来调节特定的生物途径。赖氨酸特异性组蛋白去甲基化酶LSD1在细胞生长、分化和营养代谢中起重要作用。本实验研究了天然多酚类物质白藜芦醇、姜黄素、槲皮素及其类似物对LSD1的影响。通过体外LSD1酶促实验，我们发现白藜芦醇、姜黄素和槲皮素对LSD1活性有较强的抑制作用，并且比已知的LSD1抑制剂反式-2-苯基环丙胺（TCP）更有效。白藜芦醇、姜黄素和槲皮素的新功能与它们的抗氧化性能无关，因为在类似条件下，其他抗氧化剂对LSD1没有影响。在C2C12成纤维细胞中，白藜芦醇和姜黄素能有效抑制肌原性表达和分化，这需要LSD1的参与。因此，我们的研究已经确定了LSD1作为生物活性天然化合物（如白藜芦醇、姜黄素和槲皮素）的新靶点，这一发现表明LSD1抑制至少可以部分地促进之前观察到的这些化合物的一些有益作用。
Natural polyphenols, such as resveratrol, have beneficial functions on major human diseases such as cancer, diabetes, and cardiovascular disease. Besides acting as antioxidants, some of these polyphenols can also target proteins to modulate specific biological pathways. The lysine-specific histone demethylase LSD1 plays important roles in cell growth, differentiation and nutrient metabolism. Here, we studied the effect of natural polyphenols resveratrol, curcumin, quercetin and analogs on LSD1. Using in vitro LSD1 enzymatic assays, we show that resveratrol, curcumin and quercetin displayed a potent inhibitory effect on the LSD1 activity and were more potent than the known LSD1 inhibitor trans-2-phenylcyclopropylamine (TCP). The new function of resveratrol, curcumin and quercetin is independent of their antioxidant properties, as other antioxidants had no effect on LSD1 under the similar conditions. In C2C12 fibroblasts, resveratrol and curcumin can efficiently inhibit myogenic expression and differentiation, for which LSD1 is required. Thus, our study has identified LSD1 as a novel target of bioactive natural compounds, such as resveratrol, curcumin and quercetin, and such finding suggests that LSD1 inhibition can at least partially contribute to some of the previously observed beneficial effects of these compounds.