Ceramides induce apoptosis in HeLa cells and enhance cytochrome c-induced apoptosis in Xenopus egg extracts.
Ceramide has been reported to induce typical apoptotic changes in nuclei incubated in a cell-free system, and that the addition of ceramide bypasses the requirement for mitochondria. Here, we explore the possible pathways by which ceramide induces apoptosis either in intact cells or in a cell-free system which we have developed. We found that in the cell-free system, C2-ceramide is not able to induce apoptosis in nuclei whereas cytochrome c does, but it is able to induce HeLa cells to undergo apoptosis. Ceramide is also not able to induce apoptosis when added into the cell-free system together with purified mitochondria. Further investigation showed that C2-ceramide at certain concentrations greatly increases nuclear apoptosis caused by cytochrome c in the cell-free system. From these results we conclude that the induction of apoptosis by ceramide may require intact cells in which some unknown signal transduction pathways are involved.
Jiang
Z
Z
Department of Cell Biology and Genetics, The College of Life Sciences, Peking University, Beijing, China.
Hong
X
X
Long
H
H
Hu
J
J
Zhai
Z
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014981:Xenopus
D061945:Caspase Inhibitors; D003574:Cytochrome c Group; C064769:N-acetylsphingosine; D020169:Caspases; D013110:Sphingosine