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Developmentally regulated ceramide synthase 6 promotes apoptosis in oligodendrocytes
Author(s) -
Gudz Tatyana I.,
Chudakova Daria A.,
Kindy Mark S.,
Obeid Lina M.,
Novgorodov Sergei A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.739.7
Ceramides, which are membrane sphingolipids and key mediators of cell‐stress responses, are generated by a family of (dihydro) ceramide synthases (Lass1‐6/CerS1‐6). Each ceramide synthase produces a specific subset of ceramides characterized by various acyl chains. Here, we report that brain development features significant increases in sphingomyelin, sphingosine, and most ceramide species. In contrast, C 16:0 ‐ceramide was gradually reduced and CerS6 was down‐regulated in brain tissue and in mitochondria. We examined the effect of high CerS6 expression on cell survival in primary oligodendrocyte (OL) precursor cells, which undergo apoptotic cell death during early postnatal brain development. Exposure of OLs to glutamate resulted in apoptosis that was prevented by inhibitors of de novo ceramide biosynthesis, myriocin and fumonisin B1. Knockdown of CerS6 with siRNA reduced glutamate‐triggered OL apoptosis, whereas knockdown of CerS5 had no effect: the pro‐apoptotic role of CerS6 was not stimulus‐specific. Knockdown of CerS6 with siRNA improved cell survival in response to nerve growth factor‐induced OL apoptosis. Thus, our data suggest a novel role for CerS6 in OL apoptosis during brain development. Supported by NIH/NCCR P20 RR17677 and VA Merit awards from RR&D and BLR&D Service.