Nystatin Interferes with the Effects of N-Methyl-N′-nitro-N-nitrosoguanidine on Sphingolipid Metabolism in Human FL Cells
Nystatin Interferes with the Effects of N-Methyl-N′-nitro-N-nitrosoguanidine on Sphingolipid Metabolism in Human FL Cells
复制标题
制霉菌素干扰 N-甲基-N′-硝基-N-亚硝基胍对人 FL 细胞鞘脂代谢的影响
DOI：
10.1007/s11745-008-3209-y
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发表时间：
2008
期刊：
影响因子：
1.9
通讯作者：
Jun Yang
中科院分区：
文献类型：
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作者：
Guangyi Liu;Weimin Wang;Gongping Sun;Xiaoqiong Ma;Ziyang Liu;Jun Yang
以前我们已经证明，烷化剂N-甲基-N′-硝基-N-亚硝基胍（MNNG）可以诱导受体聚集和下游信号分子NF-κB的激活，并且受体聚集与鞘脂代谢的变化有关。另一方面，多烯抗生素制霉菌素可以阻断MNNG诱导的受体聚集。在这项研究中，使用脂质组学方法，我们进一步评估制霉菌素是否影响MNNG对鞘脂代谢的影响。结果发现制霉菌素本身在一定程度上诱导人羊膜FL细胞中鞘脂谱的变化，包括一些鞘脂种类的增加或减少。有趣的是，制霉菌素可以阻断，至少部分地，由MNNG引起的鞘脂的变化。此外，制霉菌素还能部分抑制MNNG诱导的NF-κB活化。MNNG和制霉菌素都不影响丝氨酸棕榈酰转移酶、酸性鞘磷脂酶（ASM）和鞘磷脂合成酶（鞘脂生物合成途径中的关键酶）的mRNA水平。然而，MNNG可以激活ASM和中性鞘磷脂酶，而制霉菌素预孵育抑制激活。综上所述，这些数据表明制霉菌素干扰MNNG的作用，并可能通过改变鞘脂代谢而引起其功能。
Previously we have shown that an alkylating agent N-methyl-N′-nitro-N- nitrosoguanidine (MNNG) can induce receptor clustering and the activation of a downstream signal molecule NF-κB, and that the receptor clustering is associated with changes in sphingolipids metabolism. On the other hand, the polyene antibiotic nystatin can block MNNG-induced receptor clustering. In this study, using a lipidomic approach, we further evaluated whether nystatin influenced the effects of MNNG on sphingolipids metabolism. It was found that nystatin itself induced changes in the sphingolipids profile in human amnion FL cells to a certain extent, including an increase or decrease of some sphingolipid species. Interestingly, nystatin can block, at least partially, the changes of sphingolipids-induced by MNNG. In addition, nystatin can also partially inhibit the activation of NF-κB induced by MNNG. Neither MNNG nor nystatin affects the mRNA levels of serine palmitoyltransferase, acid sphingomyelinase (ASM), and sphingomyelin synthase, key enzymes in the sphingolipids biosynthesis pathway. However, MNNG can activate ASM and neutral sphingomyelinase, while nystatin preincubation inhibits the activation. Taken together, these data suggested that nystatin interferes with the effects of MNNG, and might elicit its function through altered sphingolipids metabolism.
脂质组学的最新进展：生物标志物和药物开发的进展和应用。
影响因子：
--
作者：
Han,Xianlin
通讯作者：
Han,Xianlin
N-甲基-N-硝基-N-亚硝基胍对鞘磷脂代谢影响的脂质组学研究。
影响因子：
3.7
作者：
Huang,Yun;Shen,Jing;Wang,Ting;Yu,Yan-Ke;Chen,FanqingF;Yang,Jun
通讯作者：
Yang,Jun