PKB/Akt inhibits ceramide-induced apoptosis in neuroblastoma cells by blocking apoptosis-inducing factor (AIF) translocation.
Ceramide is a sphingolipid that is abundant in the plasma membrane of neuronal cells and is thought to have regulatory roles in cell differentiation and cell death. Ceramide is known to induce apoptosis in a variety of different cell types, whereas the physiological significance of gangliosides, another class of sphingolipids, in these processes is still unclear. We examined the mechanisms of ceramide-induced cell death using a human neuroblastoma cell line. Treatment of the human neuroblastoma cell line SH-SY5Y with ceramide induced dephosphorylation of the PKB/Akt kinase and subsequent mitochondrial dysfunction. In addition, ceramide-induced neuronal cell death was not completely blocked by inhibition of caspase activity. This incomplete inhibition appeared to be attributable to the translocation of apoptosis-inducing factor to the nucleus. Furthermore, overexpression of active PKB/Akt or Bcl-2 successfully blocked ceramide-induced neuronal cell death through inhibition of the translocation of apoptosis-inducing factor.
Kim
Nam Hyun
NH
Division of Specific Organ Cancer, Research Institute, National Cancer Center, Goyang, Republic of Korea.
Kim
Kyunghoon
K
Park
Weon Seo
WS
Son
Hyeon S
HS
Bae
Youngmee
Y
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000037:antagonists & inhibitors*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*
D051033:Apoptosis Inducing Factor; D002518:Ceramides; D051057:Proto-Oncogene Proteins c-akt