Cell density-induced changes in lipid composition and intracellular trafficking
Cell density-induced changes in lipid composition and intracellular trafficking
复制标题
DOI：
10.1007/s00018-013-1441-y
复制
发表时间：
2014-03-01
影响因子：
8
通讯作者：
Sandvig, Kirsten
中科院分区：
文献类型：
--
作者：
Kavaliauskiene, Simona;Nymark, Carl-Martin;Sandvig, Kirsten
细胞密度是细胞在培养物中生长时适应其生理学的外在因素之一。然而，人们对细胞生长过程中发生的分子变化以及如何调节细胞反应知之甚少。在许多情况下，用于体外研究的抑制剂、药物或生长因子改变了细胞增殖的速率，导致对照和处理样品中的细胞密度不同。因此，为了进行全面的数据分析，必须了解细胞密度在分子水平上的含义。在这项研究中，我们已经调查了如何在细胞生长过程中的脂质成分的变化，以及它的后果运输的滋贺毒素。通过对来自17种不同脂质类别的308种脂质进行定量，我们发现，在细胞生长过程中，几种脂质的水平和种类分布发生变化，观察到的主要变化为二酰基甘油、磷脂酸、胆固醇酯和溶血磷脂酰乙醇胺。此外，滋贺毒素在高密度细胞中的结合和逆行转运减少，这导致毒素中毒减少。总之，我们的数据提供了新的信息，脂质成分的变化在细胞生长过程中的文化，以及这些变化如何可以调节细胞内运输。
Cell density is one of the extrinsic factors to which cells adapt their physiology when grown in culture. However, little is known about the molecular changes which occur during cell growth and how cellular responses are then modulated. In many cases, inhibitors, drugs or growth factors used for in vitro studies change the rate of cell proliferation, resulting in different cell densities in control and treated samples. Therefore, for a comprehensive data analysis, it is essential to understand the implications of cell density on the molecular level. In this study, we have investigated how lipid composition changes during cell growth, and the consequences it has for transport of Shiga toxin. By quantifying 308 individual lipid species from 17 different lipid classes, we have found that the levels and species distribution of several lipids change during cell growth, with the major changes observed for diacylglycerols, phosphatidic acids, cholesterol esters, and lysophosphatidylethanolamines. In addition, there is a reduced binding and retrograde transport of Shiga toxin in high density cells which lead to reduced intoxication by the toxin. In conclusion, our data provide novel information on how lipid composition changes during cell growth in culture, and how these changes can modulate intracellular trafficking.