Nystatin interferes with the effects of N-methyl-N'-nitro-N-nitrosoguanidine on sphingolipid metabolism in human FL cells.
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-kappaB, 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-kappaB 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.
Liu
Guangyi
G
Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang, 310058, China.
Wang
Weimin
W
Sun
Gongping
G
Ma
Xiaoqiong
X
Liu
Ziyang
Z
Yang
Jun
J
D000650:Amnion / Q000166:cytology; D002478:Cells, Cultured; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009761:Nystatin / Q000494:pharmacology*; D051102:Serine C-Palmitoyltransferase / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
D016328:NF-kappa B; D013107:Sphingolipids; D008769:Methylnitronitrosoguanidine; D009761:Nystatin; D051102:Serine C-Palmitoyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D013108:Sphingomyelin Phosphodiesterase