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PKB/Akt inhibits ceramide‐induced apoptosis in neuroblastoma cells by blocking apoptosis‐inducing factor (AIF) translocation
Author(s) -
Kim Nam Hyun,
Kim Kyunghoon,
Park Weon Seo,
Son Hyeon S.,
Bae Youngmee
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21344
Subject(s) - ceramide , protein kinase b , microbiology and biotechnology , apoptosis , programmed cell death , sphingolipid , lipid signaling , biology , apoptosis inducing factor , signal transduction , cancer research , chemistry , caspase , biochemistry , receptor
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. J. Cell. Biochem. 102: 1160–1170, 2007. © 2007 Wiley‐Liss, Inc.