Enhanced ceramide-induced apoptosis in ceramide kinase overexpressing cells.
We evaluated how increased levels of ceramide kinase (CerK) would impact the growth of COS-1 fibroblasts and RBL-2H3 basophils. The low CerK activity in these cells was strongly up-regulated upon recombinant expression of CerK. CerK-overexpressing COS-1 cells depended on higher concentrations of serum for their growth and displayed many filipodia. The two CerK-overexpressing cell lines were more sensitive to C2-ceramide-mediated apoptosis, and this correlated with the production of C2-ceramide-1-phosphate by CerK. This study indicates that ceramide kinase may participate in the control of cell growth, and establishes a novel assay that will be valuable for testing ceramide kinase inhibitors.
Graf
Christine
C
Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
Rovina
Philipp
P
Tauzin
Loïc
L
Schanzer
Andrea
A
Bornancin
Frédéric
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D002518:Ceramides / Q000008:administration & dosage*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*
D002518:Ceramides; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase