A lipidomic study of the effects of N-methyl-N'-nitro-N-nitrosoguanidine on sphingomyelin metabolism.

A lipidomic study of the effects of N-methyl-N'-nitro-N-nitrosoguanidine on sphingomyelin metabolism.
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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。

DOI:
10.1111/j.1745-7270.2005.00073.x
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发表时间:
2005
影响因子:
3.7
通讯作者:
Yang,Jun
Yang,Jun
中科院分区:
生物学3区
文献类型:
--
作者:
Huang,Yun;Shen,Jing;Wang,Ting;Yu,Yan-Ke;Chen,FanqingF;Yang,Jun

文献摘要

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系统生物学是一个新的和迅速发展的研究领域,其中,通过定量描述细胞的所有单个组件之间的相互作用,可以实现对生物反应的系统水平的理解。因此,它需要生物分子的高通量测量技术,例如分别用于DNA/RNA和蛋白质的基因组学和蛋白质组学方法。最近,一个新的概念,脂质组学,它利用质谱(MS)的方法进行脂质分析,已被提出。利用这种脂质组学方法,评价了N-甲基-N′-硝基-N-亚硝基胍(MNNG)对鞘磷脂(一种主要的鞘脂)代谢的影响。从细胞中提取鞘磷脂分子,并通过基质辅助激光解吸电离-飞行时间MS进行分析。结果发现,MNNG引起鞘磷脂代谢的深刻变化,包括一些新的鞘磷脂物种的出现和一些其他的消失,并且几种鞘磷脂物种的浓度也发生了变化。这伴随着酸性鞘磷脂酶(ASM)的重新分布,这是鞘磷脂代谢的关键因素。另一方面,ASM抑制剂丙咪嗪引起鞘磷脂的积累。它还防止了MNNG的一些影响,以及ASM的重新分布。总之,这些数据表明,脂质组学方法是非常有效的细胞脂质代谢的系统分析。
Systems biology is a new and rapidly developing research area in which, by quantitatively describing the interaction among all the individual components of a cell, a systems-level understanding of a biological response can be achieved. Therefore, it requires high-throughput measurement technologies for biological molecules, such as genomic and proteomic approaches for DNA/RNA and protein, respectively. Recently, a new concept, lipidomics, which utilizes the mass spectrometry (MS) method for lipid analysis, has been proposed. Using this lipidomic approach, the effects ofN-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on sphingomyelin metabolism, a major class of sphingolipids, were evaluated. Sphingomyelin molecules were extracted from cells and analyzed by matrix-assisted laser desorption ionization-time of flight MS. It was found that MNNG induced profound changes in sphingomyelin metabolism, including the appearance of some new sphingomyelin species and the disappearance of some others, and the concentrations of several sphingomyelin species also changed. This was accompanied by the redistribution of acid sphingomyelinase (ASM), a key player in sphingomyelin metabolism. On the other hand, imipramine, an inhibitor of ASM, caused the accumulation of sphingomyelin. It also prevented some of the effects of MNNG, as well as the redistribution of ASM. Taken together, these data suggested that the lipidomic approach is highly effective for the systematic analysis of cellular lipids metabolism.