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Oxyresveratrol stimulates mucin production in an NAD+-dependent manner in human intestinal goblet cells
Food and Chemical Toxicology ( IF 3.9 ) Pub Date : 2018-06-20 , DOI: 10.1016/j.fct.2018.06.039
Dahyun Hwang 1 , HyunA Jo 2 , Seong-Ho Ma 2 , Young-Hee Lim 3
Affiliation  

The intestinal mucus layer plays an important role in the management of inflammatory bowel disease. The aim of this study was to investigate the effects of oxyresveratrol (OXY), an antioxidant, on the stimulation of mucin production in human LS 174T goblet cells and the underlying mechanism thereof. OXY increased MUC2 expression at both the mRNA and protein levels. By performing two-dimensional gel electrophoresis, we found that the expression of nicotinic acid phosphoribosyltransferase1 (NaPRT1) in OXY-treated LS 174T cells was greatly increased compared with that in negative control cells. In addition, the NAD+/NADH ratio was increased in proportion to OXY in LS 174T cells. The expression of NAD+-synthesis enzymes, NaPRT1, nicotinamide riboside kinase1 (NRK1) and nicotinamide mononucleotide adenylyltransferase1 (Nmnat1) was significantly increased at both the mRNA and protein levels in OXY-treated LS 174T cells. The inhibition of NaPRT1 and NRK1 did not decrease MUC2 expression after inhibiting by small interfering RNA (siRNA)-NaPRT1 and siRNA-NRK1, respectively; however, inhibition of Nmnat by an Nmnat inhibitor decreased MUC2 expression in a dose-dependent manner. In conclusion, OXY increases NAD+ levels, resulting in the stimulation of MUC2 expression in LS 174T cells. These findings present a novel role for NAD+ in stimulation of MUC2 expression.



中文翻译:


氧化白藜芦醇以 NAD+ 依赖性方式刺激人肠道杯状细胞中粘蛋白的产生



肠道粘液层在炎症性肠病的治疗中起着重要作用。本研究的目的是探讨抗氧化剂氧化白藜芦醇 (OXY) 对刺激人 LS 174T 杯状细胞粘蛋白产生的影响及其潜在机制。 OXY 增加了 MUC2 mRNA 和蛋白质水平的表达。通过二维凝胶电泳,我们发现OXY处理的LS 174T细胞中烟酸磷酸核糖基转移酶1(NaPRT1)的表达较阴性对照细胞大大增加。此外,LS 174T 细胞中 NAD + /NADH 比率与 OXY 成比例增加。 OXY 处理的 LS 174T 细胞中,NAD +合成酶、NaPRT1、烟酰胺核苷激酶 1 (NRK1) 和烟酰胺单核苷酸腺苷酸转移酶 1 (Nmnat1) 的 mRNA 和蛋白水平表达均显着增加。分别用小干扰RNA(siRNA) -NaPRT1和siRNA- NRK1抑制后, NaPRT1NRK1的抑制不会降低MUC2的表达;然而,Nmnat 抑制剂对Nmnat的抑制以剂量依赖性方式降低MUC2表达。总之,OXY 增加 NAD +水平,从而刺激 LS 174T 细胞中 MUC2 的表达。这些发现展示了 NAD +在刺激 MUC2 表达中的新作用。

更新日期:2018-06-20
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