Siskind L J, Colombini M
Department of Biology, University of Maryland College Park, College Park, Maryland 20742, USA.
J Biol Chem. 2000 Dec 8;275(49):38640-4. doi: 10.1074/jbc.C000587200.
We report that physiological concentrations of both short- and long-chain ceramides, despite being lipids, form large stable pores in membranes. Some of these pores should be large enough to allow cytochrome c to permeate. Dihydroceramide differs from ceramide by the reduction of one double bond, and yet both its apoptogenic and channel-forming activities are greatly reduced. A structural model provides insight into how ceramides might form pores. According to a mathematical model, both the individual conductance of the channels and the overall membrane conductance are directly related to the overall concentration of ceramide in the membrane. Slight changes in concentration have dramatic effects on the size of the channels formed, providing an easy way for rapidly altering membrane permeability by changing the activity of local synthetic and catabolic enzymes. A possible role for these channels in apoptosis is discussed.
我们报告称，尽管短链和长链神经酰胺均为脂质，但生理浓度的它们可在膜中形成大的稳定孔道。其中一些孔道应足够大，以允许细胞色素c渗透。二氢神经酰胺与神经酰胺的区别在于一个双键的还原，但二者的促凋亡活性和通道形成活性均大大降低。一个结构模型有助于深入了解神经酰胺可能如何形成孔道。根据一个数学模型，通道的单个电导率和整体膜电导率均与膜中神经酰胺的总浓度直接相关。浓度的轻微变化会对形成的通道大小产生显著影响，这为通过改变局部合成酶和分解代谢酶的活性来快速改变膜通透性提供了一种简便方法。文中还讨论了这些通道在细胞凋亡中可能发挥的作用。
