Hartfield P J, Mayne G C, Murray A W
School of Biological Sciences, Flinders University of South Australia, Adelaide.
FEBS Lett. 1997 Jan 20;401(2-3):148-52. doi: 10.1016/s0014-5793(96)01460-3.
The novel lipid second messenger, ceramide, induced apoptosis in PC12 cells as determined morphologically by nuclear appearance and internucleosomal DNA fragmentation. Apoptosis was induced by exogenous C2-ceramide in a dose- and time-dependent manner. Natural ceramide and C6-ceramide had a similar effect. This response was specific since the structural analog C2-dihydroceramide and other related lipids failed to initiate apoptosis. The apoptotic effect of ceramide also depends critically on cell plating density. Furthermore, the peptide inhibitor of interleukin-1beta converting enzyme (ICE)-like proteases, Z-VAD.FMK, completely prevented the nuclear changes induced by ceramide, implicating the involvement of ICE-like protease activation in ceramide-induced apoptosis in PC12 cells.
新型脂质第二信使神经酰胺可诱导PC12细胞凋亡，这通过细胞核形态及核小体间DNA片段化进行形态学判定。外源性C2-神经酰胺以剂量和时间依赖性方式诱导凋亡。天然神经酰胺和C6-神经酰胺具有类似作用。由于结构类似物C2-二氢神经酰胺及其他相关脂质无法引发凋亡，因此该反应具有特异性。神经酰胺的凋亡效应也严重依赖于细胞接种密度。此外，白细胞介素-1β转换酶（ICE）样蛋白酶的肽抑制剂Z-VAD.FMK完全阻止了神经酰胺诱导的细胞核变化，这表明ICE样蛋白酶激活参与了神经酰胺诱导的PC12细胞凋亡。
