Ceramide triggers caspase activation during γ-radiation-induced apoptosis of human glioma cells lacking functional p53

摘要: We have previously shown that treatment of human glioma U87-MG cells expressing wild-type p53 with a DNA topoisomerase II inhibitor, etoposide resulted in ceramide-dependent apoptotic cell death. However, U87-W E6 lacking functional due to the expression papilloma virus type 16 (HPV-16) oncoprotein were resistant etoposide. In order gain insight into roles and ceramide gamma-radiation-induced death, we used vector-infected U87-LXSN cells. relatively gamma-radiation. cells, which lost p53, became susceptible radiation-induced apoptosis. Activation caspase-3, formation by acid sphingomyelinase, but not neutral associated p53-independent Radiation-induced caspase activation death modified agents affected metabolism. SR33557, an inhibitor suppressed then contrast, N-oleoylethanolamine (OE) D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), inhibit ceramidase UDP-glucose:ceramide glucosyltransferase-1, respectively, augment formation, enhanced activation. These results indicate gamma-radiation, may play important role during apoptosis p53.