Future of Toxicology - Lipidomics, an important emerging area for toxicologists: Focus on lipid oxidation products
Future of Toxicology - Lipidomics, an important emerging area for toxicologists: Focus on lipid oxidation products
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DOI：
10.1021/tx7000652
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发表时间：
2007-06-01
影响因子：
4.1
通讯作者：
Zimman, Alejandro
中科院分区：
文献类型：
--
作者：
Berliner, Judith A.;Zimman, Alejandro
脂质组学是一个重要而又未被充分研究的领域，毒物学家可以在其中发挥重要作用。当细胞暴露在有毒或无毒的介质中时，可以观察到转录、翻译、酶活性和脂质组成方面的反应。所有这些都有助于处理细胞的表型。为了测量RNA、蛋白质和脂肪的变化，有必要有分离、鉴定和定量的方法。这些变化的重要性需要通过了解所识别的分子的功能来评估。控制分子水平的代谢途径也必须是已知的。分离、鉴定和定量mRNAs的方法现在已经到位，由这些RNAs编码的蛋白质的功能也变得已知。此外，使用表达质粒和siRNA确定蛋白质功能的方法也是可用的。高通量筛选mRNAs的方法现已成为系统生物学的重要工具。一些蛋白质组学方法，如蛋白质鉴定和比较处理细胞和未处理细胞中的蛋白质组成变得更加容易。包括结构域分析和结晶学在内的确定蛋白质功能的策略正在帮助确定孤儿蛋白的功能。随着磷酸化等蛋白质修饰措施决定活性的发现，测量蛋白质活性的方法也变得更加常规。然而，相对较新的重要发现突显了新的蛋白质修饰和相互作用在控制活性方面的重要性。在这一领域仍然需要更多的方法论发展。总之，蛋白质和RNA的分离、鉴定和定量的方法都很发达，蛋白质和RNA代谢的研究也有很长的历史。然而，正如资助Lipid Maps倡议的美国国立卫生研究院(NIH)所认识到的那样，脂质组学已经落后了。脂质分析进展缓慢的原因有很多，但已经取得了重大进展，为进一步取得进展指明了道路。综上所述，虽然许多主要的细胞脂质已经被确定，但对介体的反应形成的脂质氧化产物的组成现在才被确定。使鉴定复杂化的问题是，这些脂类的活性水平非常低；因此，在进行鉴定之前，必须开发分离方法。量化是一个单独的问题，需要额外的工具和标准的制定。需要改进将正常和修饰的脂类输送到适当的细胞隔间的有效方法。主要脂质的新陈代谢已经被很好地研究出来了。对修饰脂质代谢的研究已经证明了更多
Lipidomics is an important and understudied area in which toxicologists can play an important role. When a cell is exposed to a toxic agent or a nontoxic mediator, responses are observed in transcription, translation, enzyme activity, and lipid composition. All of these contribute to the phenotype of the treated cells. To measure changes in RNA, protein, and lipid, it is necessary to have methods for their isolation, identification, and quantitation. The importance of these changes needs to be assessed by knowing the function of the molecules identified. Metabolic pathways controlling the levels of the molecules must also be known. The methods for isolation, identification, and quantitation of mRNAs are now in place, and functions of the proteins encoded by these RNAs are becoming known. Furthermore, methods for determining protein function using expression plasmids and siRNA are available. Methods for high-throughput screening of mRNAs have now become an important tool in systems biology. Some proteomic methods such as protein identification and comparison of the protein composition in treated and untreated cells are becoming more easily accessible.Strategies to determine protein function involving domain analysis and crystallography are helping to determine the function of orphan proteins. Methods to measure the activity of proteins are also becoming more routine with the discovery that measures of protein modifications such as phosphorylation determine activity. However, important relatively recent discoveries are highlighting the importance of novel protein modification and interactions in controlling activity. More methodologic development is still needed in this area. In summary, methods for protein and RNA isolation, identification, and quantitative are well-developed and there is a long history of studies of protein and RNA metabolism. However, as recognized by the NIH, which funded the Lipid Maps initiative (1), lipidomics have lagged behind. There are many reasons for the slower progress of lipid analysis, but significant progress has been made that points the way for additional progress. To summarize the problem, while many of the major cellular lipids have been identified, the composition of the lipid oxidation products that form in response to mediators are only now being identified. Complicating the identification is the problem that these lipids are active at very low levels; therefore, isolation methods must be developed before identification can be made. Quantitation is a separate problem requiring additional instrumentation and development of standards. Effective methods of delivering both normal and modified lipids to appropriate cell compartments need to be improved. The metabolism of the major lipids has been well worked out. Studies of the metabolism of modified lipids have proven more